Kidney Failure, ChronicPhase 1NCT05340426
Porcine Kidney Xenotransplantation in Patients With End-Stage Kidney Disease
A Phase 1 study testing UKidney in people with Kidney Failure, Chronic, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The mismatch between organ supply and demand results in the deaths of thousands of Americans each year. Our research group aims to solve this unmitigated health care crisis by translating advances in xenotransplantation to humans and expanding organ supply in a sustainable fashion using genetically modified pigs as a… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Kidney Failure, Chronic
- What is being tested?
- UKidney
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2024to 30 Jun 2029
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-75 years
- Body mass index (BMI) 18-40 kg/m2
- Waitlisted for kidney allotransplantation at UAB
- Dialysis dependent
- Proficient in the English language
- Presence of risk factors for
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- high wait list mortality, AND/OR
- anticipated or actual prolonged wait time on the wait list, AND/OR
- inability to access a suitable organ offer.
- Note: Examples of risk factors include high cPRA, frequent incompatible crossmatches leading to prolonged wait times, listing at an advanced age, and impending loss of dialysis access, recurrent disease in previous transplants.
- Crossmatch compatible with porcine donor
- SARS-CoV-2 vaccination in accordance with most recent CDC guidance
- Willingness to obtain other standard-of-care vaccinations for kidney transplant recipients (MMR, HBV, Herpes Zoster, etc.) and for patients receiving eculizumab (Menactra® and Bexsero®)
- Reside within a 60-minute radius of the UAB hospital (by ground transport)
Who cannot join
- Age <18y or ≥ 76y
- BMI ≤ 18 or ≥ 41 kg/m2
- Current pregnancy
- Presence of severe comorbid disease, including but not limited to uncontrolled HTN or DM (hemoglobin A1C (HgA1C) >10%), advanced cardiovascular disease, absent surgical targets for implantation, etc.
- Presence of hypercoagulable disorder
- Inability to accept a blood transfusion
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- Intolerance of immunosuppression
- History of medical non-compliance
- Presence of untreated psychiatric disease
- Significant psychosocial vulnerability and/or poor social support
- Current use/abuse of illicit drugs and/or abuse of alcohol
- History of psychiatric hospitalization
- Inability to provide informed consent
- Pre-emptive transplant
- Inability to comply with study protocols and procedures
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama Birmingham
Birmingham, Alabama, 35294
About this study
The mismatch between organ supply and demand results in the deaths of thousands of Americans each year. Our research group aims to solve this unmitigated health care crisis by translating advances in xenotransplantation to humans and expanding organ supply in a sustainable fashion using genetically modified pigs as a source of organs. We propose here a phase I clinical trial of porcine kidney xenotransplantation into 20 people with end-stage kidney disease. Source donor animals are pigs with 10 gene edits (10-GE) which attenuate immunologic harm to the kidney xenograft. 10-GE pigs are housed in a designated pathogen-free facility within 30 minutes of the transplantation center. Xenotransplantation procedures follow conventional practices currently employed in allotransplantation and comply with multiple regulatory standards to ensure ethical treatment of research subjects and source animals. Recruitment and xenotransplantation will occur over 5 years with study follow-up extending 1 year after xenotransplantation. Primary outcome variables surround patient safety, such as patient survival and the rate of zoonotic disease transmission. Secondary outcome variables include commonly used metrics of graft survival and function.
Read the detailed description
Twenty patients with ESKD listed for kidney allotransplantation at UAB will be enrolled to receive either one or two porcine kidney xenotransplants from a 10-GE pig donor, contingent on the pig's overall size at the time of procurement.
Recruitment and xenotransplantation will occur over a five-year time period. Patients will undergo follow-up of one year post-xenotransplant with study extension if graft survival exceeds one year.
Participants will undergo prospective crossmatching with a 10-GE pig to determine histocompatibility prior to xenotransplant. After performance of a negative crossmatch, procurement of the donor pig will occur in a surgical suite at the designated pathogen-free facility near the UAB campus where the donor herd is maintained.
Porcine kidney(s) will be transported under sterile and hypothermic conditions to the main UAB hospital. The porcine kidney(s) will be transplanted into the research subject in standard surgical fashion within the abdomen and immunosuppression will be administered. The induction immunosuppression regimen utilized will mirror that used in human-to-human allotransplantation; this regimen represents current standard-of-care. After transplantation, kidney health will be assessed biochemically, histologically, and radiographically. Subjects will be monitored for potential zoonotic disease transmission and blood-based chimerism as well as thrombocytopenia or indicators of consumptive coagulopathy, development of anti-human leukocyte antigen antibody/alloantibody sensitization.
FOLLOW-UP PHASE
Xenotransplant recipients are expected to remain in the hospital under close clinical surveillance by the study team and associates for approximately 1-3 weeks, pending kidney recovery and surveillance for potential complications.
Post-transplant Medications. The post-transplant immunosuppression and maintenance regimen consists of conventional agents that are routinely used in kidney allotransplantation. Although immunosuppression practices in allotransplantation can vary widely from center to center, the approach below utilizes agents and doses employed by UAB's Incompatible Kidney Transplant Program. As the ideal immunosuppression regimen for xenotransplantation has not yet been established, Investigator and team have adopted strategies used in incompatible kidney allotransplantation based on the assumption that significant antigenic variation remains between the species and antibody responses of unknown specificity below the level of detection of the crossmatch may impact later function or graft longevity.
Maintenance immunosuppression will be administered as below:
Note: Induction immunosuppression will be given at the time of xenotransplantation and will include ATG 1.5mg/kg, solumedrol 500mg, and eculizumab 1200mg. The remaining doses of ATG will be given to a total of 6mg/kg to complete induction. The ATG dosing schedule will vary depending on degree of hemolysis and/or lineage depletion, as is routinely done in allotransplantation.
Tacrolimus in divided doses daily, to a target level of 8-12 ng/mL Mycophenolate Mofetil (1000mg twice daily as a starting dose and tapered as needed per UAB incompatible kidney allotransplantation protocol) Daily prednisone, tapered from induction to a target dose of 10 mg per day. Eculizumab, 1200 mg every two weeks Investigator and study team have opted to include eculizumab as a maintenance agent to avert or attenuate complement-mediated injury of the graft. Although the 10-GE pig expresses a number of human transgenes designed to regulate complement biology, the finding of TMA in the brain-dead human recipient (*Porrett et al, AJT 2022) suggests that additional blockade of complement may be beneficial. Given that eculizumab increases the risk of infection with encapsulated bacteria, research subjects will be required to complete the FDA REMS and be vaccinated accordingly. Ciprofloxacin 500 mg twice daily (adjusted for GFR) for 6 weeks after transplantation in individuals vaccinated with meningococcal vaccine as above. Subjects will be monitored and counseled about side effects of prolonged ciprofloxacin use, such as tendonitis and tendon rupture. When eculizumab is discontinued (such as after graft removal), ciprofloxacin will be discontinued 6 weeks after the last eculizumab dose.
Thrombosis Prophylaxis: Recipients may be maintained on a heparin infusion and/or receive aspirin as clinically indicated. Subcutaneous heparin will be administered for DVT prophylaxis. Early ambulation will be encouraged.
Antimicrobial Prophylaxis: Surgical wound prophylaxis will be discontinued within 24h of exiting the operating room. Prophylaxis against opportunistic infections will be continued after transplant.
For PCP prophylaxis: Sulfamethoxazole (or Dapsone if allergic to Sulfa). This will be continued for 12 months.
For viral/CMV/HSV prophylaxis:
Valganciclovir to prevent CMV reactivation if recipient is CMV positive. This will be renally dosed and continued for 6 months post-transplant.
If recipient is CMV negative, valacylovir will be selected for HSV prophylaxis and continued for 6 months post-transplant.
Note: Although the transplantation of CMV+ donors to CMV- recipients occurs often in human allotransplantation, this situation is unlikely to occur in the setting of this trial as porcine donors in the DPF are CMV negative. Should a porcine donor test positive for CMV, prophylaxis in the recipient would be altered accordingly (i.e., valganciclovir or ganciclovir would be provided in consultation with Transplant Infectious Disease specialists)
For Candidal prophylaxis (i.e. oral thrush): Nystatin swish/swallow
Follow-up Visits and Procedures
Frequency:
Xenotransplant recipients will be closely monitored for the duration of their participation in the study. After discharge from the hospital, the study team anticipates seeing these patients in the outpatient clinic according to the table below, with additional clinic visits as needed. Recipients will have 24h access to the study team and will be extensively educated about clinical triggers (i.e., signs and symptoms of infection, myocardial infarction, etc.) to seek care. Each visit will consist of routine care for kidney transplant patients, including an assessment of medication compliance, collection of vital signs, history, a review of systems, and physical examination including examination of the surgical wound (for the first 6-8 weeks after transplantation
Post-transplant time period Clinic visit schedule 0-1 months Twice Weekly 2-3 months Weekly 3-6 months Twice Monthly 6-12 months (or study endpoint) Monthly
Protocol biopsies will occur 24h after transplant, 3 months, 6 months, and at 12 months assuming graft survival. Biopsies may be performed either percutaneously or may require an open surgical approach. Percutaneous biopsies will be performed under ultrasound guidance. Biopsy schedule may be amended for cause. Biopsies will be submitted for routine pathologic analysis (H\&E, immunofluorescence microscopy, etc.), as well as research studies. Biopsy findings will be scored using the Banff criteria.
Imaging Studies:
Ultrasound: Kidney xenograft perfusion will be monitored with ultrasound. Grafts will be studied with ultrasound daily for the first week then weekly thereafter while recipients are in the hospital. Monthly ultrasounds will be performed in the outpatient setting for the first year (or for the duration of the graft if less than one year). Schedule may be amended for cause.
Nuclear medicine scanning: Kidney perfusion scans will be performed monthly to acquire additional information about xenograft excretion and perfusion.
Laboratory Assessments:
Most of the laboratory tests below will be performed daily for the first 2 weeks after transplantation and then gradually transition to weekly and/or monthly schedules pending clinical stability of the recipient. Testing schedule may be escalated for cause. Tests will be performed on either blood or urine and are largely non-invasive or minimally invasive (such as phlebotomy). This testing schedule will largely replicate the routine monitoring of transplant recipients.
Complete blood count with differential Complete metabolic panel (including LFTs) Coagulation panel (including PT/PTT/INR) Tacrolimus level Mycophenolate level Urinalysis Urine culture 24h urine collection (Creatinine, Protein, Albumin, Urea, Sodium, Potassium, Protein Electrophoresis and Immunofixation etc.) Daily on postoperative day 1,2,3 Weekly for two weeks Monthly for first year Random urine protein Random urine creatinine Vit D 25 and Vit D 1,25 level Intact PTH Hemoglobin A1C Lipid Profile Lymphocyte profiling (e.g. CD4, CD8,CD19, CD20) Note: blood will also be analyzed in the research laboratory where higher dimensional immune profiling can be performed using multiparameter flow cytometry, single-cell RNA-sequencing, etc.) Iron, TIBC, Ferritin Samples for blood chimerism studies Immunologic monitoring Single antigen bead screening to assess for changes in anti-HLA antibody titers which may have been provoked by cross-reactivity with SLA.
Retrospective crossmatch Pathogen monitoring CMV PCR will be performed monthly for the first transplant year. Serum and urine will be tested monthly for BK virus reactivation for one year. Monitoring of donor-derived infection
- Conditions
- Kidney Failure, Chronic
- Being tested
- UKidney
- Keywords
- Pig Kidney, Porcine Kidney, End Stage Kidney Disease, UKidney
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UKidneyDevice
Also called Porcine Kidney, Xenotransplant
The intended clinical product is a kidney derived from a domestic pig that contains an intentional genomic alteration (IGA) to protect it after transplantation from the human immune response via inactivation of endogenous porcine genes responsible for expression of pig epitopes and inclusion of human transgenes to inhibit host immunogenic response.
| Study group | Role | What they receive |
|---|---|---|
| Porcine Kidney (UKidney) transplant | Experimental | In this phase I single arm study patients with acute renal failure will be transplanted with a porcine xenograft versus a human allograft-after transplantation the best practice standard of care will be followed for monitoring and immunosuppression with the exception of additional monitoring for potential porcine transmitted infections Receives: Device: UKidney |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient Survival After Porcine Transplant
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Measured: 30 days
Patient Survival After Porcine Transplant
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Measured: 90 days
Patient Survival After Porcine Transplant
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Measured: 6 months
Patient Survival After Porcine Transplant
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Measured: 12 months
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Post-op day 1
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Post-op day 2
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Post-op day 3
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Week 1
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Week 2
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 1
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 2
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 3
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 4
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 5
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 6
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 7
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 8
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 9
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 10
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 11
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Measured: Month 12
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Post-op day 1
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Post-op day 2
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Post-op day 3
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Week 1
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Week 2
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 1
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 2
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 3
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 4
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 5
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 6
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 7
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 8
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 9
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 10
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 11
Prevalence of blood based chimerism after transplantation
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Measured: Month 12
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Post-op day 1
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Post-op day 2
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Post-op day 3
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Week 1
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Week 2
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 1
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 2
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 3
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 4
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 5
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 6
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 7
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 8
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 9
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 10
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 11
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Measured: Month 12
Secondary outcomes (13)
Kidney outcomes including:
- Dialysis-free survival-patient remains off of dialysis
Measured: Through study completion, an average of 1 year
Kidney outcomes including:
- estimated glomerular filtration rate (eGFR)
Measured: Through study completion, an average of 1 year
Kidney outcomes including:
- urine output during index hospitalization
Measured: Through study completion, an average of 1 year
Kidney outcomes including:
- prevalence and degree of proteinuria
Measured: Through study completion, an average of 1 year
Kidney outcomes including:
- incidence and duration of delayed graft function (DGF)
- DGF defined as need for at least one dialysis session in first week after transplantation
Measured: Through study completion, an average of 1 year
Kidney outcomes including:
- incidence of primary non-function (PNF)
- PNF defined as dialysis dependence or creatinine clearance ≤ 20 ml/min 90 days after transplantation
Measured: Through study completion, an average of 1 year
Histologic outcomes including:
- incidence of acute cellular rejection (ACR)
- incidence of antibody-mediated rejection (AMR)
- incidence of complement deposition, etc.
- incidence of recurrent disease
Measured: Through study completion, an average of one year
Infectious outcomes including:
- incidence of surgical site infections
- incidence of hospital acquired infection (i.e. pneumonia, urinary tract infection (UTI), Central Line-Associated Blood Stream Infection (CLABSI))
- prevalence of conventional opportunistic infection (i.e. pneumocystis pneumonia (PCP), cytomegalovirus (CMV), polyomavirus (BK) etc.);
Measured: Through study completion, an average of one year
Immunologic outcomes:
- calculated panel reactive antibody (cPRA)
Measured: Through study completion, an average of one year
Cardiovascular outcomes including:
- resolution or exacerbation of hypertension (HTN), ease of blood pressure control as evidenced by type and number of anti-hypertensive medications
Measured: Through study completion, an average of one year
Cardiovascular outcomes including:
- rate of new onset diabetes after transplant (NODAT) or worsening/improvement of control of pre-existing diabetes mellitus (DM) as evidenced by medications needed for glycemic control
Measured: Through study completion, an average of one year
Cardiovascular outcomes including:
- incidence of myocardial infarction and/or stroke following xenotransplantation
Measured: Through study completion, an average of one year
Cardiovascular outcomes including:
- incidence of hypotension or other blood pressure alterations, as renin produced by the pig kidney may not be able to cleave human angiotensinogen, evidenced by type and dosage of anti-hypertensive or anti-hypotensive medications required to maintain blood pressure within normal limits of 160/80
Measured: Through study completion, an average of one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2022
- Study start31 Jan 2024 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Why it stopped: Approval to move forward with this clinical trial has not been granted by governing bodies.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase I clinical trial involving the use of a porcine kidney xenograft for transplant in place of a human kidney allograft to treat chronic renal failure in patients on dialysis
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- United Therapeutics, Lung Biotechnology PBC
- Responsible party
- Principal investigator, Jayme E Locke, University of Alabama at Birmingham
- Investigators
- Jayme E Locke, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05340426
- Sponsor's protocol ID
- IRB-300008933
- Status last verified
- Jan 2024
- First submitted
- 27 Feb 2022
- Last updated
- 1 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Bobier C, Reinhardt N, Pawlowski K. Animal rights, animal research, and the need to reimagine science. New Bioeth. 2024 Mar;30(1):63-76. doi: 10.1080/20502877.2023.2300232. Epub 2024 Jan 5.
PubMed 38182130
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Porcine Kidney Xenotransplantation in Patients With End-Stage Kidney Disease
- ClinicalTrials.gov ID
- NCT05340426
- Acronym / sponsor ID
- IRB-300008933
- Conditions
- Kidney Failure, Chronic
- Keywords
- Pig Kidney, Porcine Kidney, End Stage Kidney Disease, UKidney
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Approval to move forward with this clinical trial has not been granted by governing bodies.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- United Therapeutics, Lung Biotechnology PBC
- Study start
- 31 Jan 2024 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 22 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The mismatch between organ supply and demand results in the deaths of thousands of Americans each year. Our research group aims to solve this unmitigated health care crisis by translating advances in xenotransplantation to humans and expanding organ supply in a sustainable fashion using genetically modified pigs as a source of organs. We propose here a phase I clinical trial of porcine kidney xenotransplantation into 20 people with end-stage kidney disease. Source donor animals are pigs with 10 gene edits (10-GE) which attenuate immunologic harm to the kidney xenograft. 10-GE pigs are housed in a designated pathogen-free facility within 30 minutes of the transplantation center. Xenotransplantation procedures follow conventional practices currently employed in allotransplantation and comply with multiple regulatory standards to ensure ethical treatment of research subjects and source animals. Recruitment and xenotransplantation will occur over 5 years with study follow-up extending 1 year after xenotransplantation. Primary outcome variables surround patient safety, such as patient survival and the rate of zoonotic disease transmission. Secondary outcome variables include commonly used metrics of graft survival and function.
Detailed description
Twenty patients with ESKD listed for kidney allotransplantation at UAB will be enrolled to receive either one or two porcine kidney xenotransplants from a 10-GE pig donor, contingent on the pig's overall size at the time of procurement.
Recruitment and xenotransplantation will occur over a five-year time period. Patients will undergo follow-up of one year post-xenotransplant with study extension if graft survival exceeds one year.
Participants will undergo prospective crossmatching with a 10-GE pig to determine histocompatibility prior to xenotransplant. After performance of a negative crossmatch, procurement of the donor pig will occur in a surgical suite at the designated pathogen-free facility near the UAB campus where the donor herd is maintained.
Porcine kidney(s) will be transported under sterile and hypothermic conditions to the main UAB hospital. The porcine kidney(s) will be transplanted into the research subject in standard surgical fashion within the abdomen and immunosuppression will be administered. The induction immunosuppression regimen utilized will mirror that used in human-to-human allotransplantation; this regimen represents current standard-of-care. After transplantation, kidney health will be assessed biochemically, histologically, and radiographically. Subjects will be monitored for potential zoonotic disease transmission and blood-based chimerism as well as thrombocytopenia or indicators of consumptive coagulopathy, development of anti-human leukocyte antigen antibody/alloantibody sensitization.
FOLLOW-UP PHASE
Xenotransplant recipients are expected to remain in the hospital under close clinical surveillance by the study team and associates for approximately 1-3 weeks, pending kidney recovery and surveillance for potential complications.
Post-transplant Medications. The post-transplant immunosuppression and maintenance regimen consists of conventional agents that are routinely used in kidney allotransplantation. Although immunosuppression practices in allotransplantation can vary widely from center to center, the approach below utilizes agents and doses employed by UAB's Incompatible Kidney Transplant Program. As the ideal immunosuppression regimen for xenotransplantation has not yet been established, Investigator and team have adopted strategies used in incompatible kidney allotransplantation based on the assumption that significant antigenic variation remains between the species and antibody responses of unknown specificity below the level of detection of the crossmatch may impact later function or graft longevity.
Maintenance immunosuppression will be administered as below:
Note: Induction immunosuppression will be given at the time of xenotransplantation and will include ATG 1.5mg/kg, solumedrol 500mg, and eculizumab 1200mg. The remaining doses of ATG will be given to a total of 6mg/kg to complete induction. The ATG dosing schedule will vary depending on degree of hemolysis and/or lineage depletion, as is routinely done in allotransplantation.
Tacrolimus in divided doses daily, to a target level of 8-12 ng/mL Mycophenolate Mofetil (1000mg twice daily as a starting dose and tapered as needed per UAB incompatible kidney allotransplantation protocol) Daily prednisone, tapered from induction to a target dose of 10 mg per day. Eculizumab, 1200 mg every two weeks Investigator and study team have opted to include eculizumab as a maintenance agent to avert or attenuate complement-mediated injury of the graft. Although the 10-GE pig expresses a number of human transgenes designed to regulate complement biology, the finding of TMA in the brain-dead human recipient (*Porrett et al, AJT 2022) suggests that additional blockade of complement may be beneficial. Given that eculizumab increases the risk of infection with encapsulated bacteria, research subjects will be required to complete the FDA REMS and be vaccinated accordingly. Ciprofloxacin 500 mg twice daily (adjusted for GFR) for 6 weeks after transplantation in individuals vaccinated with meningococcal vaccine as above. Subjects will be monitored and counseled about side effects of prolonged ciprofloxacin use, such as tendonitis and tendon rupture. When eculizumab is discontinued (such as after graft removal), ciprofloxacin will be discontinued 6 weeks after the last eculizumab dose.
Thrombosis Prophylaxis: Recipients may be maintained on a heparin infusion and/or receive aspirin as clinically indicated. Subcutaneous heparin will be administered for DVT prophylaxis. Early ambulation will be encouraged.
Antimicrobial Prophylaxis: Surgical wound prophylaxis will be discontinued within 24h of exiting the operating room. Prophylaxis against opportunistic infections will be continued after transplant.
For PCP prophylaxis: Sulfamethoxazole (or Dapsone if allergic to Sulfa). This will be continued for 12 months.
For viral/CMV/HSV prophylaxis:
Valganciclovir to prevent CMV reactivation if recipient is CMV positive. This will be renally dosed and continued for 6 months post-transplant.
If recipient is CMV negative, valacylovir will be selected for HSV prophylaxis and continued for 6 months post-transplant.
Note: Although the transplantation of CMV+ donors to CMV- recipients occurs often in human allotransplantation, this situation is unlikely to occur in the setting of this trial as porcine donors in the DPF are CMV negative. Should a porcine donor test positive for CMV, prophylaxis in the recipient would be altered accordingly (i.e., valganciclovir or ganciclovir would be provided in consultation with Transplant Infectious Disease specialists)
For Candidal prophylaxis (i.e. oral thrush): Nystatin swish/swallow
Follow-up Visits and Procedures
Frequency:
Xenotransplant recipients will be closely monitored for the duration of their participation in the study. After discharge from the hospital, the study team anticipates seeing these patients in the outpatient clinic according to the table below, with additional clinic visits as needed. Recipients will have 24h access to the study team and will be extensively educated about clinical triggers (i.e., signs and symptoms of infection, myocardial infarction, etc.) to seek care. Each visit will consist of routine care for kidney transplant patients, including an assessment of medication compliance, collection of vital signs, history, a review of systems, and physical examination including examination of the surgical wound (for the first 6-8 weeks after transplantation
Post-transplant time period Clinic visit schedule 0-1 months Twice Weekly 2-3 months Weekly 3-6 months Twice Monthly 6-12 months (or study endpoint) Monthly
Protocol biopsies will occur 24h after transplant, 3 months, 6 months, and at 12 months assuming graft survival. Biopsies may be performed either percutaneously or may require an open surgical approach. Percutaneous biopsies will be performed under ultrasound guidance. Biopsy schedule may be amended for cause. Biopsies will be submitted for routine pathologic analysis (H\&E, immunofluorescence microscopy, etc.), as well as research studies. Biopsy findings will be scored using the Banff criteria.
Imaging Studies:
Ultrasound: Kidney xenograft perfusion will be monitored with ultrasound. Grafts will be studied with ultrasound daily for the first week then weekly thereafter while recipients are in the hospital. Monthly ultrasounds will be performed in the outpatient setting for the first year (or for the duration of the graft if less than one year). Schedule may be amended for cause.
Nuclear medicine scanning: Kidney perfusion scans will be performed monthly to acquire additional information about xenograft excretion and perfusion.
Laboratory Assessments:
Most of the laboratory tests below will be performed daily for the first 2 weeks after transplantation and then gradually transition to weekly and/or monthly schedules pending clinical stability of the recipient. Testing schedule may be escalated for cause. Tests will be performed on either blood or urine and are largely non-invasive or minimally invasive (such as phlebotomy). This testing schedule will largely replicate the routine monitoring of transplant recipients.
Complete blood count with differential Complete metabolic panel (including LFTs) Coagulation panel (including PT/PTT/INR) Tacrolimus level Mycophenolate level Urinalysis Urine culture 24h urine collection (Creatinine, Protein, Albumin, Urea, Sodium, Potassium, Protein Electrophoresis and Immunofixation etc.) Daily on postoperative day 1,2,3 Weekly for two weeks Monthly for first year Random urine protein Random urine creatinine Vit D 25 and Vit D 1,25 level Intact PTH Hemoglobin A1C Lipid Profile Lymphocyte profiling (e.g. CD4, CD8,CD19, CD20) Note: blood will also be analyzed in the research laboratory where higher dimensional immune profiling can be performed using multiparameter flow cytometry, single-cell RNA-sequencing, etc.) Iron, TIBC, Ferritin Samples for blood chimerism studies Immunologic monitoring Single antigen bead screening to assess for changes in anti-HLA antibody titers which may have been provoked by cross-reactivity with SLA.
Retrospective crossmatch Pathogen monitoring CMV PCR will be performed monthly for the first transplant year. Serum and urine will be tested monthly for BK virus reactivation for one year. Monitoring of donor-derived infection
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase I clinical trial involving the use of a porcine kidney xenograft for transplant in place of a human kidney allograft to treat chronic renal failure in patients on dialysis
| Arm | Type | Receives |
|---|---|---|
| Porcine Kidney (UKidney) transplant | Experimental | Device: UKidneyIn this phase I single arm study patients with acute renal failure will be transplanted with a porcine xenograft versus a human allograft-after transplantation the best practice standard of care will be followed for monitoring and immunosuppression with the exception of additional monitoring for potential porcine transmitted infections |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Ages 18-75 years
- Body mass index (BMI) 18-40 kg/m2
- Waitlisted for kidney allotransplantation at UAB
- Dialysis dependent
- Proficient in the English language
Key exclusion criteria (15 listed)
- Age <18y or ≥ 76y
- BMI ≤ 18 or ≥ 41 kg/m2
- Current pregnancy
- Presence of severe comorbid disease, including but not limited to uncontrolled HTN or DM (hemoglobin A1C (HgA1C) >10%), advanced cardiovascular disease, absent surgical targets for implantation, etc.
- Presence of hypercoagulable disorder
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UKidneyAlso: Porcine Kidney, XenotransplantThe intended clinical product is a kidney derived from a domestic pig that contains an intentional genomic alteration (IGA) to protect it after transplantation from the human immune response via inactivation of endogenous porcine genes responsible for expression of pig epitopes and inclusion of human transgenes to inhibit host immunogenic response. | Device | Porcine Kidney (UKidney) transplant |
Primary outcome
Patient Survival After Porcine Transplant
Time frame: 30 days
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Patient Survival After Porcine Transplant
Time frame: 90 days
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Patient Survival After Porcine Transplant
Time frame: 6 months
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Patient Survival After Porcine Transplant
Time frame: 12 months
These time points align with both biologic events that occur after transplantation (i.e., immune reconstitution after T cell depletion) as well as conventional transplant outcome metrics used by regulatory authorities (i.e., Organ Procurement and Transplantation Network, United Network for Organ Sharing)
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Post-op day 1
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Post-op day 2
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Post-op day 3
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Week 1
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Week 2
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 1
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 2
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 3
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 4
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 5
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 6
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 7
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 8
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 9
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 10
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 11
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of thrombocytopenia or indicators of consumptive coagulopathy after transplant with porcine kidney
Time frame: Month 12
Consumptive coagulopathy has been observed in some non-human primate models of transplant with a pig kidney. Thrombocytopenia was also observed in the UAB brain-dead recipient but could not be attributed to the porcine kidney given the altered physiology of brain death.
Prevalence of blood based chimerism after transplantation
Time frame: Post-op day 1
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Post-op day 2
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Post-op day 3
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Week 1
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Week 2
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 1
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 2
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 3
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 4
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 5
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 6
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 7
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 8
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 9
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 10
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 11
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Prevalence of blood based chimerism after transplantation
Time frame: Month 12
The presence of donor-derived cells in the blood stream of a transplant recipient can either portend graft versus host disease (GVHD) or be diagnostic of the disease
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Post-op day 1
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Post-op day 2
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Post-op day 3
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Week 1
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Week 2
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 1
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 2
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 3
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 4
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 5
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 6
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 7
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 8
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 9
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 10
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 11
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
Development of anti-human leukocyte antigen (HLA) antibody/alloantibody sensitization after transplant with a porcine kidney
Time frame: Month 12
It is currently unknown whether porcine kidney xenografts will ever function sufficiently to become a destination therapy for patients with ESKD. However, if porcine kidney xenografts have modest longevity, there may be benefit to temporary rescue from dialysis. Porcine kidney xenografts may then act as a bridge to human allotransplantation. Thus, there is the need to determine whether porcine kidney xenografts provoke the development of anti-HLA antibody and sensitize recipients against human allografts. Such sensitization may prevent xenograft recipients from ever receiving a human allotransplant, and the frequency of this event must be determined in order to counsel patients effectively about the risks of participating in additional trials of xenotransplantation.
13 secondary outcomes
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Kidney outcomes including:
Time frame: Through study completion, an average of 1 year
Histologic outcomes including:
Time frame: Through study completion, an average of one year
Infectious outcomes including:
Time frame: Through study completion, an average of one year
Immunologic outcomes:
Time frame: Through study completion, an average of one year
Cardiovascular outcomes including:
Time frame: Through study completion, an average of one year
Cardiovascular outcomes including:
Time frame: Through study completion, an average of one year
Cardiovascular outcomes including:
Time frame: Through study completion, an average of one year
Cardiovascular outcomes including:
Time frame: Through study completion, an average of one year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2024.
- Derived from this study: PubMed 38182130Bobier C, Reinhardt N, Pawlowski K. Animal rights, animal research, and the need to reimagine science. New Bioeth. 2024 Mar;30(1):63-76. doi: 10.1080/20502877.2023.2300232. Epub 2024 Jan 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jayme E Locke, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing UKidney in people with Kidney Failure, Chronic, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient Survival After Porcine Transplant (time frame: 30 days). The study lists 55 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05340426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2024.