Clinical Trial: Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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 containi
Sponsor: Beijing 302 Hospital

Current Primary Outcome:

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Serum AST [ Time Frame: 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 ]
  • Serum immunoglobulin G (IgG) [ Time Frame: 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 ]
  • MELD score [ Time Frame: 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
  • 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


Original Secondary Outcome: Same as current

Information By: Beijing 302 Hospital

Dates:
Date Received: August 5, 2012
Date Started: October 2011
Date Completion: October 2014
Last Updated: May 30, 2013
Last Verified: May 2013