Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

NCT ID: NCT01661842

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

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2014-10-31

Brief Summary

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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

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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.

Conditions

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Autoimmune Hepatitis

Keywords

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Autoimmune Hepatitis Mesenchymal stem cells serum albumin serum Tbil serum immunoglobulin G(IgG)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

conventional plus UC-MSC treatment

Intervention Type OTHER

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 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.

Group Type EXPERIMENTAL

Conventional plus placebo treatment

Intervention Type OTHER

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

Interventions

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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.

Intervention Type OTHER

Conventional plus placebo treatment

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Beijing 302 Hospital

OTHER

Sponsor Role lead

Responsible Party

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Fu-Sheng Wang

Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fu-Sheng Wang, professor

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

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Beijing 302 Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Fu-Sheng Wang, professor

Role: CONTACT

Phone: 86-10-63879735

Email: [email protected]

Zheng Zhang, Doctor

Role: CONTACT

Phone: 86-10-63879735

Email: [email protected]

Facility Contacts

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Fu-Sheng Wang, professor

Role: primary

Lifeng Wang, Doctor

Role: backup

References

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Czaja AJ. Advances in the current treatment of autoimmune hepatitis. Dig Dis Sci. 2012 Aug;57(8):1996-2010. doi: 10.1007/s10620-012-2151-2. Epub 2012 Apr 3.

Reference Type BACKGROUND
PMID: 22476586 (View on PubMed)

Montano-Loza AJ, Carpenter HA, Czaja AJ. Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease. Hepatology. 2007 Oct;46(4):1138-45. doi: 10.1002/hep.21787.

Reference Type BACKGROUND
PMID: 17668882 (View on PubMed)

Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des. 2011;17(29):3120-40. doi: 10.2174/138161211798157568.

Reference Type BACKGROUND
PMID: 21902661 (View on PubMed)

Gossard AA, Lindor KD. Autoimmune hepatitis: a review. J Gastroenterol. 2012 May;47(5):498-503. doi: 10.1007/s00535-012-0586-z. Epub 2012 Apr 17.

Reference Type BACKGROUND
PMID: 22526272 (View on PubMed)

Malekzadeh Z, Haghazali S, Sepanlou SG, Vahedi H, Merat S, Sotoudeh M, Nasseri-Moghaddam S, Malekzadeh R. Clinical features and long term outcome of 102 treated autoimmune hepatitis patients. Hepat Mon. 2012 Feb;12(2):92-9. doi: 10.5812/hepatmon.808. Epub 2012 Feb 29.

Reference Type BACKGROUND
PMID: 22509185 (View on PubMed)

Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res. 2012 Feb;35(2):213-21. doi: 10.1007/s12272-012-0202-z. Epub 2012 Feb 28.

Reference Type BACKGROUND
PMID: 22370776 (View on PubMed)

Holbro A, Abinun M, Daikeler T. Management of autoimmune diseases after haematopoietic stem cell transplantation. Br J Haematol. 2012 May;157(3):281-90. doi: 10.1111/j.1365-2141.2012.09070.x. Epub 2012 Feb 24.

Reference Type BACKGROUND
PMID: 22360687 (View on PubMed)

Other Identifiers

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Beijing302-006

Identifier Type: -

Identifier Source: org_study_id