Human Mesenchymal Stem Cells Induce Liver Transplant Tolerance

NCT ID: NCT01690247

Last Updated: 2013-05-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2015-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Evidence of Liver Transplantation

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

mesenchymal stem cells liver transplantation clinical trial rejection

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Conventional plus UC-MSC

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

Group Type EXPERIMENTAL

Conventional plus UC-MSC

Intervention Type DRUG

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 placebo

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.

Group Type PLACEBO_COMPARATOR

Conventional plus placebo

Intervention Type DRUG

Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Conventional plus UC-MSC

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.

Intervention Type DRUG

Conventional plus placebo

Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Immunosuppressive agents plus umbilical cord stem cells Immunosuppressive agents plus saline

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Written informed consent.
2. Patients must be between the ages of 18 and 70 years and meet the criteria for liver transplantation.
3. Patient is receiving the first liver transplant.
4. Patient is receiving a liver transplant only.
5. Negative pregnancy test (female patients in fertile age).
6. Willing to comply with the study visits.

Exclusion Criteria

1. Previously received or is receiving an organ transplant other than a liver.
2. Vital organs failure (Cardiac, Renal or Respiratory, et al).
3. Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant.
4. Currently receiving any immunosuppressive agent.
5. Clinically active bacterial, fungal, viral or parasitic infection.
6. Pregnant or lactating women.
7. Other candidates who are judged to be not applicable to this study by investigators.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Beijing 302 Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Fu-Sheng Wang

Research Center for Biotherapy

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Fu-Sheng Wang, PHD

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Beijing 302 Hospital

Beijing, , China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Fu-Sheng Wang, PHD

Role: CONTACT

Phone: 86-10-63879735

Email: [email protected]

Ming Shi, PHD

Role: CONTACT

Phone: 86-10-63879735

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Fu-Sheng Wang, PHD

Role: primary

Ming Shi, PHD

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type RESULT
PMID: 22436957 (View on PubMed)

Perico 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.

Reference Type RESULT
PMID: 20930086 (View on PubMed)

Le 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.

Reference Type RESULT
PMID: 18468541 (View on PubMed)

Shi 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.

Reference Type RESULT
PMID: 21352202 (View on PubMed)

Zhang 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.

Reference Type RESULT
PMID: 22320928 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Beijing302-008

Identifier Type: -

Identifier Source: org_study_id