Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis

Autoimmune Hepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01661842
• Other study ID #: Beijing302-006
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: August 5, 2012
• Last updated: May 30, 2013
• Start date: October 2011
• Est. completion date: October 2014

Study information

• Verified date: May 2013
• Source: Beijing 302 Hospital
• Contact: Fu-Sheng Wang, professor
• Phone: 86-10-63879735
• Email: fswang302[@]163.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Autoimmune

Intervention

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

Locations

Country	Name	City	State
China	Beijing 302 Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing 302 Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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. Review. — View Citation

Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des. 2011;17(29):3120-40. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Liver Histology change		baseline and 96 weeks	No
Primary	Serum alanine aminotransferase (ALT)		0,12, 24, 36, 48, 72, 96 weeks after treatment	No
Secondary	Serum AST		At baseline and at week 12, 24, 36, 48, 72, 96	No
Secondary	Serum Tbil		At baseline and at week 12, 24, 36, 48, 72, 96	No
Secondary	Serum immunoglobulin G (IgG)		At baseline and at week 12, 24, 36, 48, 72, 96	No
Secondary	Serum ?-globulin		At baseline and at week 12, 24, 36, 48, 72, 96	No
Secondary	MELD score		At base line and at week 12, 24, 36, 48, 72, 96	No
Secondary	Number of participants with treatment side effects	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	No
Secondary	Number of participants with improvement of clinical symptoms	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	No