Trial record 10 of 15 for:    "Hepatitis, Autoimmune"

Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Beijing 302 Hospital
Sponsor:
Information provided by (Responsible Party):
Fu-Sheng Wang, Beijing 302 Hospital
ClinicalTrials.gov Identifier:
NCT01661842
First received: August 5, 2012
Last updated: May 30, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Autoimmune Hepatitis
Other: conventional plus UC-MSC treatment
Other: Conventional plus placebo treatment
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Autoimmune Liver Disease

Resource links provided by NLM:


Further study details as provided by Beijing 302 Hospital:

Primary Outcome Measures:
  • Liver Histology change [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
  • Serum alanine aminotransferase (ALT) [ Time Frame: 0,12, 24, 36, 48, 72, 96 weeks after treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum AST [ Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
  • Serum Tbil [ Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
  • Serum immunoglobulin G (IgG) [ Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
  • Serum γ-globulin [ Time Frame: At baseline and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
  • MELD score [ Time Frame: At base line and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
  • Number of participants with treatment side effects [ Time Frame: At base line and at week 12, 24, 36, 48, 72, 96 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    diffuse arthralgias, fatigue, generalized malaise, jaundice, abdominal pain, nausea, and loss of appetite


Estimated Enrollment: 100
Study Start Date: October 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01661842

Contacts
Contact: Fu-Sheng Wang, professor 86-10-63879735 ext 2015.12 fswang302@163.com
Contact: Zheng Zhang, Doctor 86-10-63879735 ext 2015.12 Zhangzheng1975@yahoo.com.cn

Locations
China, Beijing
Beijing 302 Hospital Recruiting
Beijing, Beijing, China, 100039
Contact: Fu-Sheng Wang, professor    86-10-63879735 ext 2015.12    fswang302@163.com   
Contact: Lifeng Wang, Doctor    86-10-63879735 ext 2015.12    wanglf76@gmail.com   
Principal Investigator: Fu-Sheng Wang, Professor         
Sponsors and Collaborators
Beijing 302 Hospital
Investigators
Principal Investigator: Fu-Sheng Wang, professor Beijing 302 Hospital
  More Information

Publications:
Responsible Party: Fu-Sheng Wang, Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology, Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT01661842     History of Changes
Other Study ID Numbers: Beijing302-006
Study First Received: August 5, 2012
Last Updated: May 30, 2013
Health Authority: China: Ministry of Health

Keywords provided by Beijing 302 Hospital:
Autoimmune Hepatitis
Mesenchymal stem cells
serum albumin
serum Tbil
serum immunoglobulin G(IgG)

Additional relevant MeSH terms:
Hepatitis, Autoimmune
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepatitis, Chronic
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 22, 2014