Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

May 30, 2013 updated by: Fu-Sheng Wang, Beijing 302 Hospital

Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Autoimmune Liver Disease

Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Disease presentation is varied but typically is based on characteristic aminotransferase elevations, histological abnormalities, elevated levels of serum globulins, and the presence of one or more autoantibodies. Two types of juvenile AIH have been identified according to seropositivity for smooth muscle and /or antinuclear antibody (AIH type 1) or liver kidney microsomal antibody (AIH type 2). Standard therapy in clinic consists of a combination of corticosteroids and azathioprine, which displays the efficacy in 80% of patients. However, 7% of patients deteriorate despite compliance with the standard corticosteroid regiments (treatment failure),13% of patients improve but not to a degree that satisfies remission criteria (incomplete response), 13% of patients develop serious drug-induced complications, and 50%-86% of patients will relapse after drug withdrawal. These serious drawbacks counterbalance the benefits of conventional therapy, and they are compelling reasons to refine current treatment strategies and pursue alternative therapies. UC-MSC has been the application for the treatment of several severe autoimmune diseases, such as immune thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis. In this study, the safety and efficacy of UC-MSC transplantation for AIH patients will be evaluated.

Study Overview

Detailed Description

Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver characterized by elevation of IgG, presence of characteristic autoantibodies, and histological feature of interface hepatitis. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. However, current treatment strategies are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. Alternative medical therapy may be need for AIH.

The potential for stem cells to differentiate into hepatocytes cells was recently confirmed. In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been applicated in the clinic for treat several human disease such as GVHD, cardiac injury and brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as immune thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.

The purpose of this study is to learn whether and how UC-MSC can improve the disease condition in patients with autoimmune hepatitis (AIH). This study will also look at how well UC-MSC is tolerated and its safety in AIH patients

Participants in the study will be randomly assigned to one of two treatment arms:

Arm A: Participants will receive 12 weeks of UC-MSC treatment plus conventional treatment (combination of corticosteroids and azathioprine) Arm B: Participants will receive 12 weeks of placebo plus conventional treatment. (combination of corticosteroids and azathioprine) UC-MSC will be prepared according to standard procedures and is collected in plastic bags containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell therapy, patients are followed up at week 12, 24, 36, 48, 72, 96. The evaluation of some clinical parameters such as the level of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-globulin, total bilirubin (TB), prothrombin time (PT), albumin (ALB), prealbumin (PA) and IgG, are detected at these time points. MELD score, Liver histology, treatment side effects, relapse rate and clinical symptoms were also observed simultaneously.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100039
        • Recruiting
        • Beijing 302 Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Written informed consent
  2. Autoimmune hepatitis (according to the criteria defined by the international autoimmune hepatitis Group ,Hepatology, 2008;48:169-176)
  3. Negative pregnancy test (female patients in fertile age)

Exclusion Criteria:

  1. Hepatocellular carcinoma or other Malignancies
  2. Pregnant or lactating women
  3. Viral Hepatitis ( HAV,HBV,HCV, et al )
  4. Vital organs failure (Cardiac, Renal or Respiratory, et al)
  5. Sepsis
  6. Active thrombosis in the portal or hepatic veins

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Conventional plus UC-MSC treatment

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 96 study visit.

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.
Experimental: Conventional plus placebo treatment
Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 96 study visit.
Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Liver Histology change
Time Frame: baseline and 96 weeks
baseline and 96 weeks
Serum alanine aminotransferase (ALT)
Time Frame: 0,12, 24, 36, 48, 72, 96 weeks after treatment
0,12, 24, 36, 48, 72, 96 weeks after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum AST
Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96
At baseline and at week 12, 24, 36, 48, 72, 96
Serum Tbil
Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96
At baseline and at week 12, 24, 36, 48, 72, 96
Serum immunoglobulin G (IgG)
Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96
At baseline and at week 12, 24, 36, 48, 72, 96
Serum γ-globulin
Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96
At baseline and at week 12, 24, 36, 48, 72, 96
MELD score
Time Frame: At base line and at week 12, 24, 36, 48, 72, 96
At base line and at week 12, 24, 36, 48, 72, 96
Number of participants with treatment side effects
Time Frame: At base line and at week 12, 24, 36, 48, 72, 96
weight gain, acne, facial rounding, dorsal hump formation, hirsutism, osteopenia and diabetes mellitus, et al
At base line and at week 12, 24, 36, 48, 72, 96
Number of participants with improvement of clinical symptoms
Time Frame: At base line and at week 12, 24, 36, 48, 72, 96
diffuse arthralgias, fatigue, generalized malaise, jaundice, abdominal pain, nausea, and loss of appetite
At base line and at week 12, 24, 36, 48, 72, 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Anticipated)

October 1, 2014

Study Completion (Anticipated)

October 1, 2014

Study Registration Dates

First Submitted

August 5, 2012

First Submitted That Met QC Criteria

August 9, 2012

First Posted (Estimate)

August 10, 2012

Study Record Updates

Last Update Posted (Estimate)

May 31, 2013

Last Update Submitted That Met QC Criteria

May 30, 2013

Last Verified

May 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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