Type 1 Diabetes MellitusNCT01049633
B-Lymphocyte Immunotherapy in Islet Transplantation for Initial Islet Graft Failure
A study testing Allogeneic Pancreatic Islet Cells, Sirolimus and Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Allogeneic Pancreatic Islet Cells, Sirolimus and Basiliximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Enrolled in clinical trial DAIT CIT-05 (NCT00468442)
- Islet graft failure: absent stimulated C-peptide (<0.3ng/mL) in response to mixed meal tolerance test
Who cannot join
- Untreated proliferative diabetic retinopathy
- Blood Pressure: systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg
- Measured glomerular filtration rate (GFR) using iohexol < 80ml/min/1.73m^2 Strict vegetarians with a calculated GFR < 70ml/min/1.73m^2
- Presence or history of macroalbuminuria > 300mg/g of creatinine
- Presence or history of panel-reactive anti-HLA antibodies above background by flow cytometry
- For female participants: Positive Pregnancy Test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 3 months after discontinuation. For male participants: intent to procreate during the duration of the study or within 3 months after discontinuation or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant, Depo-Provera and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
Show all 30Show fewer
- Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a positive skin test or clinical presentation, or under treatment for suspected TB. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection. Positive tests are otherwise not acceptable, even in the absence of any active infection at the time of evaluation.
- Negative screen for Epstein-Barr Virus (EBV) by IgG determination
- Invasive aspergillus, histoplasmosis, or coccidiomycosis infection within one year prior to study enrollment
- Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
- Known active alcohol or substance abuse
- Anemia (Hgb < 11 g/dL),neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL)
- A history of Factor V deficiency
- Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after transplantation (low-dose aspirin treatment is allowed) or patients with an International Normalized Ratio (INR) >1.5
- Severe co-existing cardiac disease, characterized by any one of these conditions:
- recent myocardial infarction (within past 6 months)
- evidence of ischemia on functional cardiac exam within the last year
- left ventricular ejection fraction <30%
- Persistent elevation of liver function tests (LFTs) at the time of study entry (e.g., persistent SGOT (AST), SGPT (ALT), Alk Phos or total bilirubin, with values >1.5 times normal upper limits
- Symptomatic cholecystolithiasis
- Acute or chronic pancreatitis
- Symptomatic peptic ulcer disease
- Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications
- Hyperlipidemia despite medical therapy (fasting LDL cholesterol > 130 mg/dL, treated or untreated; and/or fasting triglycerides > 200 mg/dL)
- Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only
- Use of any investigational agents within 4 weeks of enrollment
- Administration of live attenuated vaccine(s) within 2 months of enrollment
- Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial, such as chronic central neurologic disease
- Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment
- A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and the transplant occurred more that 6 months prior to enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: B-Lymphocyte Immunotherapy in Islet Transplantation: Single Subject Modification to Calcineurin-Inhibitor Based Immunosuppression for Initial Islet Graft (CIT-0501)
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Read the detailed description
Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Allogeneic Pancreatic Islet Cells, Sirolimus, Basiliximab, Tacrolimus, Antibacterial, Antifungal, and Antiviral Prophylaxis
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness, Islet transplantation
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic Pancreatic Islet CellsBiological
200mL sterile suspension of allogeneic human pancreatic islets
SirolimusDrug
Dosed to maintain whole blood 24-hr trough levels 10-15ng/mL for first 3 months and 8-12ng/mL thereafter daily. Sirolimus is used to prevent transplant rejection.
BasiliximabBiological
20mg intravenously (IV) 2hrs prior to islet infusion and on Day 4 post-transplant. Basiliximab is used to prevent transplant rejection
TacrolimusDrug
Initial dose of 0.015mg/kg p.o. daily on Day 1 post transplant, and adjusted to maintain 12-hr trough levels 3-6ng/mL. Tacrolimus lowers the risk of organ rejection
Antibacterial, Antifungal, and Antiviral ProphylaxisDrug
Broad spectrum antimicrobial prophylaxis administered preoperatively
Trimethoprim/sulfamethoxazoleDrug
Also called Septra SS
80mg/400mg by mouth once a day starting on Day 1 for duration of the study follow-up. This medication is used to prevent bacterial infections.
ClotrimazoleDrug
Also called Mycelex Troche
1 troche by mouth 4 times daily starting two days prior to transplant until 3 months after the transplant. This medication is used to prevent fungal infections.
ValganciclovirDrug
Also called Valcyte
450mg dose by mouth once a day starting two days pre-transplant and increasing to 900 mg once a day by Day 12 and continuing for 14 weeks post-transplant. This medication is used to prevent cytomegalovirus infections.
HeparinDrug
Also called Anticoagulation and Hematological Agent
70U/kg body weight of recipient given with islet infusion, followed by 3U/kg/hr for the next 4hrs. From 5th through 48th hr post-transplant heparin will be titrated to achieve and maintain a Partial Thromboplastin Time (PTT) of 50-60 seconds. This medication is used to prevent the formation of blood clots.
EnoxaparinDrug
Also called Lovenox; Anticoagulation and Hematological Agent
30mg subcutaneously twice a day from 48 hrs post-transplant through Day 7 post-transplant. This medication is used to prevent the formation of blood clots.
PentoxifyllineDrug
Also called Anticoagulation and Hematological Agent
400mg slow release tablet by mouth three times a day beginning 2 days prior to transplant and continue for 7 days post transplant. This medication improves blood flow.
AspirinDrug
Also called ASA, Anticoagulation and Hematological Agent
81mg enteric coated aspirin by mouth every night, starting 24hrs post-transplant. This medication prevents blood clots.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Expanded access
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01049633
- Sponsor's protocol ID
- DAIT CIT-0501
- Status last verified
- Jun 2014
- First submitted
- 12 Jan 2010
- Last updated
- 11 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B-Lymphocyte Immunotherapy in Islet Transplantation: Single Subject Modification to Calcineurin-Inhibitor Based Immunosuppression for Initial Islet Graft (CIT-0501)
- ClinicalTrials.gov ID
- NCT01049633
- Acronym / sponsor ID
- DAIT CIT-0501
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Insulin dependence, Hypoglycemia, Hypoglycemia unawareness, Islet transplantation
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- First posted
- 14 Jan 2010 (estimated)
- 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.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
Detailed description
Type 1 diabetes is commonly treated with the administration of insulin, either by multiple insulin injections or by a continuous supply of insulin through a wearable pump. Insulin therapy allows long-term survival in individuals with type 1 diabetes; however, it does not guarantee constant normal blood sugar control. Because of this, long-term type 1 diabetic survivors often develop vascular complications, such as diabetic retinopathy, an eye disease that can cause poor vision and blindness, and diabetic nephropathy, a kidney disease that can lead to kidney failure. Some individuals with type 1 diabetes develop hypoglycemia unawareness, a life-threatening condition that is not easily treatable with medication and is characterized by reduced or absent warning signals for hypoglycemia. For such individuals, pancreas or pancreatic islet transplantation are possible treatment options. Insulin independence among islet transplant recipients tends to decline over time. New strategies aimed at promoting engraftment of transplanted islets are needed to improve the clinical outcomes associated with this procedure.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Enrolled in clinical trial DAIT CIT-05 (NCT00468442)
- Islet graft failure: absent stimulated C-peptide (<0.3ng/mL) in response to mixed meal tolerance test
Key exclusion criteria (30 listed)
- Untreated proliferative diabetic retinopathy
- Blood Pressure: systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg
- Measured glomerular filtration rate (GFR) using iohexol < 80ml/min/1.73m^2 Strict vegetarians with a calculated GFR < 70ml/min/1.73m^2
- Presence or history of macroalbuminuria > 300mg/g of creatinine
- Presence or history of panel-reactive anti-HLA antibodies above background by flow cytometry
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 |
|---|---|---|
| Allogeneic Pancreatic Islet Cells200mL sterile suspension of allogeneic human pancreatic islets | Biological | – |
| SirolimusDosed to maintain whole blood 24-hr trough levels 10-15ng/mL for first 3 months and 8-12ng/mL thereafter daily. Sirolimus is used to prevent transplant rejection. | Drug | – |
| Basiliximab20mg intravenously (IV) 2hrs prior to islet infusion and on Day 4 post-transplant. Basiliximab is used to prevent transplant rejection | Biological | – |
| TacrolimusInitial dose of 0.015mg/kg p.o. daily on Day 1 post transplant, and adjusted to maintain 12-hr trough levels 3-6ng/mL. Tacrolimus lowers the risk of organ rejection | Drug | – |
| Antibacterial, Antifungal, and Antiviral ProphylaxisBroad spectrum antimicrobial prophylaxis administered preoperatively | Drug | – |
| Trimethoprim/sulfamethoxazoleAlso: Septra SS80mg/400mg by mouth once a day starting on Day 1 for duration of the study follow-up. This medication is used to prevent bacterial infections. | Drug | – |
| ClotrimazoleAlso: Mycelex Troche1 troche by mouth 4 times daily starting two days prior to transplant until 3 months after the transplant. This medication is used to prevent fungal infections. | Drug | – |
| ValganciclovirAlso: Valcyte450mg dose by mouth once a day starting two days pre-transplant and increasing to 900 mg once a day by Day 12 and continuing for 14 weeks post-transplant. This medication is used to prevent cytomegalovirus infections. | Drug | – |
| HeparinAlso: Anticoagulation and Hematological Agent70U/kg body weight of recipient given with islet infusion, followed by 3U/kg/hr for the next 4hrs. From 5th through 48th hr post-transplant heparin will be titrated to achieve and maintain a Partial Thromboplastin Time (PTT) of 50-60 seconds. This medication is used to prevent the formation of blood clots. | Drug | – |
| EnoxaparinAlso: Lovenox; Anticoagulation and Hematological Agent30mg subcutaneously twice a day from 48 hrs post-transplant through Day 7 post-transplant. This medication is used to prevent the formation of blood clots. | Drug | – |
| PentoxifyllineAlso: Anticoagulation and Hematological Agent400mg slow release tablet by mouth three times a day beginning 2 days prior to transplant and continue for 7 days post transplant. This medication improves blood flow. | Drug | – |
| AspirinAlso: ASA, Anticoagulation and Hematological Agent81mg enteric coated aspirin by mouth every night, starting 24hrs post-transplant. This medication prevents blood clots. | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Link provided by the sponsor.
Related trials for Type 1 Diabetes Mellitus
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Allogeneic Pancreatic Islet Cells, Sirolimus and Basiliximab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 2 inclusion and 30 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: status not confirmed, as of the sponsor's last update on 11 Jun 2014. 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.
Are results available for this study?
Results are not available in the source record.
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.
Where can I read the original study information?
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 11 Jun 2014.