- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01661842
Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis
Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Autoimmune Liver Disease
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100039
- Recruiting
- Beijing 302 Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent
- Autoimmune hepatitis (according to the criteria defined by the international autoimmune hepatitis Group ,Hepatology, 2008;48:169-176)
- Negative pregnancy test (female patients in fertile age)
Exclusion Criteria:
- Hepatocellular carcinoma or other Malignancies
- Pregnant or lactating women
- Viral Hepatitis ( HAV,HBV,HCV, et al )
- Vital organs failure (Cardiac, Renal or Respiratory, et al)
- Sepsis
- Active thrombosis in the portal or hepatic veins
Study Plan
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
Sponsor
Publications and helpful links
General Publications
- 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.
- 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.
- Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des. 2011;17(29):3120-40. doi: 10.2174/138161211798157568.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Beijing302-006
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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