Safety and Efficacy Study of Regulatory T Cells in Treating Autoimmune Hepatitis

Study Overview
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Brief Summary
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Separated and expanded the CD4+CD25+CD127- Tregs from peripheral blood of autoimmune hepatitis patients and administrate the cells (5 x 106 cells/kg) into patients.

Detailed Description
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The trial will be carried out in autoimmune patients. The investigators will isolate CD4(cluster of differentiation)+CD25(cluster of differentiation25)+CD127(cluster of differentiation127)- Tregs from these patients, and expand them with IL(interleukin)-2 retinoid acid and anti-CD3(cluster of differentiation 3) /CD28(cluster of differentiation 28) beads. The patients will be subsequently treated with single infusion of CD4+CD25+CD127- Tregs (10-20 x 106 cells/kg). In the clinical trials, the investigators will monitor the number of Tregs in patients at different periods, and to test their suppressive functions in vitro. Also the function and biopsy of liver will be processed to determine the efficacy of Treg therapy.

Official Title
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Phase 1 Clinical Trial Using Regulatory T Cells as Individualized Medicine to Evaluate the Safety and Efficacy in Autoimmune Hepatitis

Conditions
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Autoimmune Diseases

Intervention / Treatment
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* Biological: Regulatory T cells


Participation Criteria
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Eligibility Criteria
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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 Moderately active disease under standard treatment Exclusion Criteria: Hepatocellular carcinoma or other Malignancies Pregnant or lactating women Vital organs failure (Cardiac, Renal or Respiratory, et al) Sepsis Active thrombosis in the portal or hepatic veins Concomitant psychiatric disease or any other chronic illness or drug-abuse that could interfere with the ability to comply with the protocol or to give informed consent Surgery during the last 2 months or surgery planned during the study, Participation in other biomedical research in the last 3 months or planned during the study.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regulatory T cells<br>CD4(cluster of differentiation)+CD25+CD127- T cells isolated from peripheral blood mononuclear cells were be expanded with GMP(Good Manufacturing Practice) anti-CD3/CD28 coated beads in the presence of IL-2 and all-trans retinoid acid. | Biological: Regulatory T cells<br>* Regulatory t cells will be injected back to autoimmune hepatitis patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical remission(serum levels of alanine aminotransferase, aspartate aminotransferase and Total bilirubin within normal ranges) |  | 12 months | 
| immunology remission(=serum levels of T cell subsets, immune globulin, and complement within normal ranges) and lack of other side effects. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of biochemical remission 2 times increase of serum levels of alanine aminotransferase, aspartate aminotransferase and Total bilirubin. |  | 12 months | 
| Suspected rejection detected by clinical feature or biopsy. |  | 12 months | 
| Incidence of 2 times increase of immunology related level(serum levels of T cell subsets,immune globulin) or present other side effects. |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autoimmune Diseases, Treg