Liver FailurePhase 1/2NCT01429038
Mesenchymal Stem Cells After Renal or Liver Transplantation
A Phase 1/2 study testing Mesenchymal Stem Cells in people with Liver Failure and Kidney Failure, run by University of Liege at 1 site in Belgium.
Trial summary
The immune system of a patient can attack the liver or the kidney received from a donor (organ rejection). This can be prevented by treating these patients long-life with immunosuppressive drugs. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Failure, Kidney Failure
- What is being tested?
- Mesenchymal Stem Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Feb 2012to 11 Mar 2019
- Phase
- Phase 1/2
- 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
- Male or female patients between 18 and 75 years of age, who will undergo first Kidney Transplantation or whole Liver Transplantation from a cadaveric or donation after cardiac death (DCD) organ donor;
- Fertile female patients must use a reliable contraception method;
- Informed consent given by patient or his/next of kin if the patient is unable to give informed consent, for the complete (MSC + follow-up) or partial(no MSC + follow-up) study;
- Successful liver/kidney transplantation, demonstration of organ function (improvement of INR in liver recipients and of creatinine in kidney recipients at 24-36h) and normal graft vasculature at Doppler examination.
Who cannot join
- Past history of malignant disease, with the exception of hepatocarcinoma within the Milan criteria for the Liver Transplantation patients;
- Active uncontrolled infection;
- HIV or HCV positive;
- EBV-negative;
- Retransplantation;
- Combined transplantation;
Show all 11Show fewer
- Living related transplantation or split liver transplantation;
- Autoimmune disease or expected impossibility to wean immunosuppression (Liver Transplantation) or corticosteroids (Kidney Transplantation);
- Endotracheal intubation;
- Postoperative cardiovascular instability, active hemorrhage, or any other serious clinical complication between transplantation and evaluation for suitability for MSC infusion;
- For Kidney Transplantation: panel reactive antibodies (PRA) >50%.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Infusion of Third-party Mesenchymal Stem Cells After Renal or Liver Transplantation. A Phase I-II, Open-label, Clinical Study
The immune system of a patient can attack the liver or the kidney received from a donor (organ rejection). This can be prevented by treating these patients long-life with immunosuppressive drugs. Unfortunately, these drugs lead to numerous side effects and fail to prevent the rejection occurring months later after the transplantation (chronic rejection). Recently, it has been shown that a particular type of cells present in the bone marrow, namely Mesenchymal Stem Cells (MSC), when injected to a patient, suppress its immune system and increase success rates of blood cells transplantation. This outcome opens doors to investigate the potential of these cells to provide a valuable tool for improving solid organ transplantation without the need of high concentration of immunosuppressive drugs. The present project aims at evaluating the safety and tolerability of MSC administration after liver or kidney transplantation.
Read the detailed description
The present project aims at evaluating the safety and tolerability of third party MSC administration after liver or kidney organ transplantation. Ten patients undergoing liver transplantation and 10 patients undergoing kidney transplantation will be included in the experimental arm to receive a single infusion of MSC. The outcome of each of these 2 subgroups will be compared with that of similar control patients undergoing liver or kidney transplantation but who will not receive MSC.
Liver and kidney transplanted patients will receive standard immunosuppressive therapy, TAC-MMF-steroïds and TAC-MMF-steroïds plus an IL-2-R antibody respectively. Patients enrolled in the experimental arms will be infused with a single dose of 1,5-3,0 10E6 MSC/kg, 3(+/-2) days after the transplantation.
Weaning of immunosuppression will be attempted from month 6 in liver transplant patients who did not present a rejection episode and show normal graft function and graft biopsy.
Kidney transplant patients will continue standard immunosuppressive therapy indefinitely.
Male or female (>18 years) individuals unrelated to the recipient or the graft donor will be MSC donors. MSC donors need to fulfill generally accepted criteria for allogeneic HSC donation.
- Conditions
- Liver Failure, Kidney Failure
- Being tested
- Mesenchymal Stem Cells
- Keywords
- end-stage, liver diseases, cirrhosis, cancer, fulminant hepatic failure, metabolic hepatic diseases, congenital hepatic diseases, renal diseases
- Medical subject headings
- Liver Failure, Renal Insufficiency, Liver Diseases, Fibrosis, Neoplasms, Liver Failure, Acute, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem CellsBiological
Also called MSC
Third party MSC 1,5-3,010E6/kg. No HLA matching between MSC donor and the recipient or the liver/kidney donor. One infusion at day 3+/-2.
| Study group | Role | What they receive |
|---|---|---|
| MSC Liver Transplantation | Experimental | Patients undergoing a first liver transplantation. Beside receiving standard liver tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2 Receives: Biological: Mesenchymal Stem Cells |
| MSC Kidney Transplantation | Experimental | Patients undergoing a first kidney transplantation. Beside receiving standard kidney tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids associated with ant-IL-2 antibodies), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2. Receives: Biological: Mesenchymal Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infusional toxicity
Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.
Measured: Within 24 hours of infusion
Incidence of infections (bacterial, viral, fungal, parasitic) and cancers
- Incidence, timing and severity of any infection (bacterial, viral, fungal, parasitic) (blood hemoculture, urine culture, PCR CMV, PCR BK virus at month 1,2,3)
- Incidence, timing and severity of malignant disease (Posttransplant lymphoproliferative disorder or other)
Measured: Continuously over 2 years
Secondary outcomes (6)
Patient and graft survivals
Measured: Continuously over 2 years
Effects of MSC on graft function
- Liver Transplantation: bilirubin, INR, transaminases, GGT, at day 7, months 1, 3, 6, 9, 12.
- Kidney Transplanttaion: number of post transplant hemodialysis, creatinine at day 7, months 1, 3, 6, 9, 12.
Measured: over 1 year
Biopsy-proven (Banff classification) rejection rates
At months 3, 6, 9, 12.
Measured: over 1 year
Feasibility and safety of weaning or decreasing immunosuppression
Decision points at months 3, 6, 9, 12.
Measured: continuously over 2 years
Recipient's immune function
To evaluate recipient's immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies).
Measured: over 1 year
Anti-MSC donor HLA antibodies.
To evaluate the potential development of anti-MSC donor HLA antibodies.
Measured: over 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2011 (estimated)
- Study start1 Feb 2012
- Primary completion11 Mar 2019
- Study completion11 Mar 2019
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 Liver FailureStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yves Beguin, University of Liege
- Investigators
- Yves Beguin, MD, PhD, Principal investigator, CHU-ULg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429038
- Sponsor's protocol ID
- TJT1106P1
- Status last verified
- Jun 2022
- First submitted
- 1 Sep 2011
- Last updated
- 14 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Detry O, Vandermeulen M, Delbouille MH, Somja J, Bletard N, Briquet A, Lechanteur C, Giet O, Baudoux E, Hannon M, Baron F, Beguin Y. Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study. J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.
PubMed 28284916
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of Third-party Mesenchymal Stem Cells After Renal or Liver Transplantation. A Phase I-II, Open-label, Clinical Study
- ClinicalTrials.gov ID
- NCT01429038
- Acronym / sponsor ID
- TJT1106P1
- Conditions
- Liver Failure, Kidney Failure
- Keywords
- end-stage, liver diseases, cirrhosis, cancer, fulminant hepatic failure, metabolic hepatic diseases, congenital hepatic diseases, renal diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Study start
- 1 Feb 2012 (actual)
- Primary completion
- 11 Mar 2019 (actual)
- Study completion
- 11 Mar 2019 (actual)
- First posted
- 5 Sep 2011 (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.
The immune system of a patient can attack the liver or the kidney received from a donor (organ rejection). This can be prevented by treating these patients long-life with immunosuppressive drugs. Unfortunately, these drugs lead to numerous side effects and fail to prevent the rejection occurring months later after the transplantation (chronic rejection). Recently, it has been shown that a particular type of cells present in the bone marrow, namely Mesenchymal Stem Cells (MSC), when injected to a patient, suppress its immune system and increase success rates of blood cells transplantation. This outcome opens doors to investigate the potential of these cells to provide a valuable tool for improving solid organ transplantation without the need of high concentration of immunosuppressive drugs. The present project aims at evaluating the safety and tolerability of MSC administration after liver or kidney transplantation.
Detailed description
The present project aims at evaluating the safety and tolerability of third party MSC administration after liver or kidney organ transplantation. Ten patients undergoing liver transplantation and 10 patients undergoing kidney transplantation will be included in the experimental arm to receive a single infusion of MSC. The outcome of each of these 2 subgroups will be compared with that of similar control patients undergoing liver or kidney transplantation but who will not receive MSC.
Liver and kidney transplanted patients will receive standard immunosuppressive therapy, TAC-MMF-steroïds and TAC-MMF-steroïds plus an IL-2-R antibody respectively. Patients enrolled in the experimental arms will be infused with a single dose of 1,5-3,0 10E6 MSC/kg, 3(+/-2) days after the transplantation.
Weaning of immunosuppression will be attempted from month 6 in liver transplant patients who did not present a rejection episode and show normal graft function and graft biopsy.
Kidney transplant patients will continue standard immunosuppressive therapy indefinitely.
Male or female (>18 years) individuals unrelated to the recipient or the graft donor will be MSC donors. MSC donors need to fulfill generally accepted criteria for allogeneic HSC donation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSC Liver Transplantation | Experimental | Biological: Mesenchymal Stem CellsPatients undergoing a first liver transplantation. Beside receiving standard liver tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2 |
| MSC Kidney Transplantation | Experimental | Biological: Mesenchymal Stem CellsPatients undergoing a first kidney transplantation. Beside receiving standard kidney tranplantation care (antibacterial and viral prophylactic treatments as well as a standard immunosuppressive regime i.e. tacrolimus, mycophenolate mofetil and steroids associated with ant-IL-2 antibodies), patients will be infused with 1,5-3,0 10E6 MSC/kg on postoperative day 3+/-2. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female patients between 18 and 75 years of age, who will undergo first Kidney Transplantation or whole Liver Transplantation from a cadaveric or donation after cardiac death (DCD) organ donor;
- Fertile female patients must use a reliable contraception method;
- Informed consent given by patient or his/next of kin if the patient is unable to give informed consent, for the complete (MSC + follow-up) or partial(no MSC + follow-up) study;
- Successful liver/kidney transplantation, demonstration of organ function (improvement of INR in liver recipients and of creatinine in kidney recipients at 24-36h) and normal graft vasculature at Doppler examination.
Key exclusion criteria (11 listed)
- Past history of malignant disease, with the exception of hepatocarcinoma within the Milan criteria for the Liver Transplantation patients;
- Active uncontrolled infection;
- HIV or HCV positive;
- EBV-negative;
- Retransplantation;
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 |
|---|---|---|
| Mesenchymal Stem CellsAlso: MSCThird party MSC 1,5-3,010E6/kg. No HLA matching between MSC donor and the recipient or the liver/kidney donor. One infusion at day 3+/-2. | Biological | MSC Kidney Transplantation, MSC Liver Transplantation |
Primary outcome
Infusional toxicity
Time frame: Within 24 hours of infusion
Incidence, timing and severity of any clinical complication related to MSC infusion, including pulmonary events or immune reactions.
Incidence of infections (bacterial, viral, fungal, parasitic) and cancers
Time frame: Continuously over 2 years
* Incidence, timing and severity of any infection (bacterial, viral, fungal, parasitic) (blood hemoculture, urine culture, PCR CMV, PCR BK virus at month 1,2,3) * Incidence, timing and severity of malignant disease (Posttransplant lymphoproliferative disorder or other)
6 secondary outcomes
Patient and graft survivals
Time frame: Continuously over 2 years
Effects of MSC on graft function
Time frame: over 1 year
Biopsy-proven (Banff classification) rejection rates
Time frame: over 1 year
Feasibility and safety of weaning or decreasing immunosuppression
Time frame: continuously over 2 years
Recipient's immune function
Time frame: over 1 year
Anti-MSC donor HLA antibodies.
Time frame: over 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2022.
- Derived from this study: PubMed 28284916Detry O, Vandermeulen M, Delbouille MH, Somja J, Bletard N, Briquet A, Lechanteur C, Giet O, Baudoux E, Hannon M, Baron F, Beguin Y. Infusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study. J Hepatol. 2017 Jul;67(1):47-55. doi: 10.1016/j.jhep.2017.03.001. Epub 2017 Mar 9.
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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.
Yves Beguin, MD, PhD principal investigator
CHU-ULg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal Stem Cells in people with Liver Failure and Kidney Failure, run by University of Liege at 1 site in Belgium.
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 4 inclusion and 11 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: finished, as of the sponsor's last update on 14 Jun 2022. 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 Belgium. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Infusional toxicity (time frame: Within 24 hours of infusion). The study lists 2 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 NCT01429038, 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 14 Jun 2022.