Evidence of Liver TransplantationPhase 1NCT01690247
Human Mesenchymal Stem Cells Induce Liver Transplant Tolerance
A Phase 1 study testing Conventional plus UC-MSC in people with Evidence of Liver Transplantation, run by Beijing 302 Hospital at 1 site in China.
Trial summary
Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. Despite the ability of current immunosuppressive agents to reduce the incidence of acute rejection, the rate of acute rejection reaches to 20-50% after liver transplantation. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Evidence of Liver Transplantation
- What is being tested?
- Conventional plus UC-MSC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Feb 2012to Feb 2015
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Patients must be between the ages of 18 and 70 years and meet the criteria for liver transplantation.
- Patient is receiving the first liver transplant.
- Patient is receiving a liver transplant only.
- Negative pregnancy test (female patients in fertile age).
- Willing to comply with the study visits.
Who cannot join
- Previously received or is receiving an organ transplant other than a liver.
- Vital organs failure (Cardiac, Renal or Respiratory, et al).
- Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant.
- Currently receiving any immunosuppressive agent.
- Clinically active bacterial, fungal, viral or parasitic infection.
- Pregnant or lactating women.
- Other candidates who are judged to be not applicable to this study by investigators.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing 302 Hospital
Beijing, 100039
Fu-Sheng Wang, PHD, 86-10-63879735 ext. 2015.12, fswang302@163.com
Ming Shi, PHD, 86-10-63879735 ext. 2015.12, shiming302@sina.com
About this study
Official title: Human Umbilical Cord Mesenchymal Stem Cell Induce Liver Allografts Tolerance
Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. Despite the ability of current immunosuppressive agents to reduce the incidence of acute rejection, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term toxicity associated with current regimens for liver transplant recipients now is increasingly being perceived as an unmet clinical need. Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Here, we evaluate umbilical cord derived MSC (UC-MSC) as an alternative immunosuppressive agents for liver transplanted patients, and examine if UC-MSC could improve the recovery of liver function.
Read the detailed description
Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. The current immunosuppressive agents reduce the incidence of acute cellular rejection; however, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term side effects of these regimens now has become a major challenge for liver transplant recipients and is increasingly being perceived as an unmet clinical need, for example, increases in the incidence of bacterial, viral infections, nephrotoxicity with chronic renal impairment, de novo diabetes mellitus, hyperlipidemia, arterial hypertension, cardiovascular disease, osteoporosis, neurotoxicity, hematological toxicity.
Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Current clinical trails demonstrated that the use of autologous bone marrow MSC (BM-MSC) for renal transplanted patients resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function. Compared with BM-MSC, umbilical cord derived MSC (UC-MSC) may be the better choice for clinical application. One main reason is that the collection of BM-MSC from liver transplanted patients would be harmful for the patients. Moreover, the proliferative abilities of BM-MSC from patients with liver disease are deficient, whereas, UC-MSC can be obtained from discarded umbilical cords and can be produced on a larger scale. Our and other studies reported that the infusion of human UC-MSC are feasible and can improve liver function of liver fibrosis and liver failure.
The purpose of this study is to learn whether and how UC-MSC can improve the conditions in liver transplanted patients. This study will also look at how well UC-MSC is tolerated and its safety in liver transplanted patients.
Participants in the study will be randomly assigned to one of two treatment arms:
Arm A: Participants will receive 12 weeks of standard regular immunosuppressive agents plus UC-MSC treatment. Arm B: Participants will receive 12 weeks of standard regular immunosuppressive agents plus placebo. UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anti coagulant. MSCs are given via i.v. under sonography monitoring. After UC-MSC transfusion, patients are followed up at week 4, 8, 12, 24, 36 and 48, and the evaluation of liver function recovery was performed.
- Conditions
- Evidence of Liver Transplantation
- Being tested
- Conventional plus UC-MSC, Conventional plus placebo
- Keywords
- mesenchymal stem cells, liver transplantation, clinical trial, rejection
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional plus UC-MSCDrug
Also called Immunosuppressive agents plus umbilical cord stem cells
Received conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks.
Conventional plus placeboDrug
Also called Immunosuppressive agents plus saline
Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Conventional plus UC-MSC | Experimental | Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit Receives: Drug: Conventional plus UC-MSC |
| Conventional plus placebo | Placebo comparator | Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit. Receives: Drug: Conventional plus placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate of acute rejection and early liver function recovery
Measured: 48 weeks
Secondary outcomes (1)
Patient and graft survival, and prevalence of adverse events
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2012 (estimated)
- Study startFeb 2012
- Primary completionFeb 2014 (estimated)
- Study completionFeb 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Evidence of Liver TransplantationStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing 302 Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fu-Sheng Wang, Beijing 302 Hospital
- Investigators
- Fu-Sheng Wang, PHD, Principal investigator, Beijing 302 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01690247
- Sponsor's protocol ID
- Beijing302-008
- Status last verified
- May 2013
- First submitted
- 19 Sep 2012
- Last updated
- 31 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tan J, Wu W, Xu X, Liao L, Zheng F, Messinger S, Sun X, Chen J, Yang S, Cai J, Gao X, Pileggi A, Ricordi C. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA. 2012 Mar 21;307(11):1169-77. doi: 10.1001/jama.2012.316.
PubMed 22436957Perico N, Casiraghi F, Introna M, Gotti E, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Marasa M, Golay J, Noris M, Remuzzi G. Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol. 2011 Feb;6(2):412-22. doi: 10.2215/CJN.04950610. Epub 2010 Oct 7.
PubMed 20930086Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.
PubMed 18468541Shi M, Liu ZW, Wang FS. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol. 2011 Apr;164(1):1-8. doi: 10.1111/j.1365-2249.2011.04327.x. Epub 2011 Feb 24.
PubMed 21352202Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y, Yu S, Geng H, Jin L, Lau GK, Wang FS. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2:112-20. doi: 10.1111/j.1440-1746.2011.07024.x.
PubMed 22320928
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Umbilical Cord Mesenchymal Stem Cell Induce Liver Allografts Tolerance
- ClinicalTrials.gov ID
- NCT01690247
- Acronym / sponsor ID
- Beijing302-008
- Conditions
- Evidence of Liver Transplantation
- Keywords
- mesenchymal stem cells, liver transplantation, clinical trial, rejection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Beijing 302 HospitalUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Feb 2014 (estimated)
- Study completion
- Feb 2015 (estimated)
- First posted
- 21 Sep 2012 (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.
Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. Despite the ability of current immunosuppressive agents to reduce the incidence of acute rejection, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term toxicity associated with current regimens for liver transplant recipients now is increasingly being perceived as an unmet clinical need. Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Here, we evaluate umbilical cord derived MSC (UC-MSC) as an alternative immunosuppressive agents for liver transplanted patients, and examine if UC-MSC could improve the recovery of liver function.
Detailed description
Liver transplantation is the only lifesaving intervention for patients with end-stage liver diseases. The current immunosuppressive agents reduce the incidence of acute cellular rejection; however, the rate of acute rejection reaches to 20-50% after liver transplantation. Furthermore, the long-term side effects of these regimens now has become a major challenge for liver transplant recipients and is increasingly being perceived as an unmet clinical need, for example, increases in the incidence of bacterial, viral infections, nephrotoxicity with chronic renal impairment, de novo diabetes mellitus, hyperlipidemia, arterial hypertension, cardiovascular disease, osteoporosis, neurotoxicity, hematological toxicity.
Mesenchymal stem cells (MSC) appeared to be effective in regulating the invoked immune response in setting such as tissue injury, transplantation, and autoimmunity, and have been used successfully to treat graft versus host disease and show immune modulation function both in vitro and in vivo and may help in repairing damaged tissue(s). Current clinical trails demonstrated that the use of autologous bone marrow MSC (BM-MSC) for renal transplanted patients resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function. Compared with BM-MSC, umbilical cord derived MSC (UC-MSC) may be the better choice for clinical application. One main reason is that the collection of BM-MSC from liver transplanted patients would be harmful for the patients. Moreover, the proliferative abilities of BM-MSC from patients with liver disease are deficient, whereas, UC-MSC can be obtained from discarded umbilical cords and can be produced on a larger scale. Our and other studies reported that the infusion of human UC-MSC are feasible and can improve liver function of liver fibrosis and liver failure.
The purpose of this study is to learn whether and how UC-MSC can improve the conditions in liver transplanted patients. This study will also look at how well UC-MSC is tolerated and its safety in liver transplanted patients.
Participants in the study will be randomly assigned to one of two treatment arms:
Arm A: Participants will receive 12 weeks of standard regular immunosuppressive agents plus UC-MSC treatment. Arm B: Participants will receive 12 weeks of standard regular immunosuppressive agents plus placebo. UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anti coagulant. MSCs are given via i.v. under sonography monitoring. After UC-MSC transfusion, patients are followed up at week 4, 8, 12, 24, 36 and 48, and the evaluation of liver function recovery was performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional plus UC-MSC | Experimental | Drug: Conventional plus UC-MSCParticipants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit |
| Conventional plus placebo | Placebo comparator | Drug: Conventional plus placeboParticipants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 48 study visit. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written informed consent.
- Patients must be between the ages of 18 and 70 years and meet the criteria for liver transplantation.
- Patient is receiving the first liver transplant.
- Patient is receiving a liver transplant only.
- Negative pregnancy test (female patients in fertile age).
Key exclusion criteria (7 listed)
- Previously received or is receiving an organ transplant other than a liver.
- Vital organs failure (Cardiac, Renal or Respiratory, et al).
- Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant.
- Currently receiving any immunosuppressive agent.
- Clinically active bacterial, fungal, viral or parasitic infection.
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 |
|---|---|---|
| Conventional plus UC-MSCAlso: Immunosuppressive agents plus umbilical cord stem cellsReceived conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks. | Drug | Conventional plus UC-MSC |
| Conventional plus placeboAlso: Immunosuppressive agents plus salineReceived conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks. | Drug | Conventional plus placebo |
Primary outcome
Incidence rate of acute rejection and early liver function recovery
Time frame: 48 weeks
1 secondary outcome
Patient and graft survival, and prevalence of adverse events
Time frame: 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2013.
- Results publication: PubMed 22436957Tan J, Wu W, Xu X, Liao L, Zheng F, Messinger S, Sun X, Chen J, Yang S, Cai J, Gao X, Pileggi A, Ricordi C. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA. 2012 Mar 21;307(11):1169-77. doi: 10.1001/jama.2012.316.
- Results publication: PubMed 20930086Perico N, Casiraghi F, Introna M, Gotti E, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Marasa M, Golay J, Noris M, Remuzzi G. Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol. 2011 Feb;6(2):412-22. doi: 10.2215/CJN.04950610. Epub 2010 Oct 7.
- Results publication: PubMed 18468541Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.
- Results publication: PubMed 21352202Shi M, Liu ZW, Wang FS. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol. 2011 Apr;164(1):1-8. doi: 10.1111/j.1365-2249.2011.04327.x. Epub 2011 Feb 24.
- Results publication: PubMed 22320928Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y, Yu S, Geng H, Jin L, Lau GK, Wang FS. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2:112-20. doi: 10.1111/j.1440-1746.2011.07024.x.
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.
Fu-Sheng Wang, PHD principal investigator
Beijing 302 Hospital
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 Conventional plus UC-MSC in people with Evidence of Liver Transplantation, run by Beijing 302 Hospital at 1 site in China.
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 6 inclusion and 7 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 31 May 2013. 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 China. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fu-Sheng Wang, PHD (86-10-63879735 ext. 2015.12, fswang302@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence rate of acute rejection and early liver function recovery (time frame: 48 weeks). 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 NCT01690247, which also lists 5 linked publications.
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 31 May 2013.