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Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

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ClinicalTrials.gov Identifier: NCT01661842
Recruitment Status : Unknown
Verified May 2013 by Fu-Sheng Wang, Beijing 302 Hospital.
Recruitment status was:  Recruiting
First Posted : August 10, 2012
Last Update Posted : May 31, 2013
Sponsor:
Information provided by (Responsible Party):
Fu-Sheng Wang, Beijing 302 Hospital

Tracking Information
First Submitted Date  ICMJE August 5, 2012
First Posted Date  ICMJE August 10, 2012
Last Update Posted Date May 31, 2013
Study Start Date  ICMJE October 2011
Estimated Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2012)
  • 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 Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01661842 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2012)
  • 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 Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis
Official Title  ICMJE 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 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Autoimmune Hepatitis
Intervention  ICMJE
  • Other: conventional plus UC-MSC treatment
    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.
  • Other: Conventional plus placebo treatment
    Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks
Study Arms  ICMJE
  • 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.

    Intervention: Other: conventional plus UC-MSC treatment
  • 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.
    Intervention: Other: Conventional plus placebo treatment
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 9, 2012)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2014
Estimated Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01661842
Other Study ID Numbers  ICMJE Beijing302-006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fu-Sheng Wang, Beijing 302 Hospital
Study Sponsor  ICMJE Beijing 302 Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fu-Sheng Wang, professor Beijing 302 Hospital
PRS Account Beijing 302 Hospital
Verification Date May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP