Clinical trial NCT02704338: Safety and Efficacy Study of Regulatory T Cells in Treating Autoimmune Hepatitis
Official title: Phase 1 Clinical Trial Using Regulatory T Cells as Individualized Medicine to Evaluate the Safety and Efficacy in Autoimmune Hepatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Autoimmune Diseases
Keywords: Autoimmune Diseases, Treg
Lead sponsor: Nanjing Medical University
Sponsor class: OTHER
First posted: 2016-03-10
Enrollment: 30
Sex: ALL
Minimum age (years): 10
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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
4. Moderately active disease under standard treatment

Exclusion Criteria:

1. Hepatocellular carcinoma or other Malignancies
2. Pregnant or lactating women
3. Vital organs failure (Cardiac, Renal or Respiratory, et al)
4. Sepsis
5. Active thrombosis in the portal or hepatic veins
6. 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
7. Surgery during the last 2 months or surgery planned during the study,
8. Participation in other biomedical research in the last 3 months or planned during the study.

Primary outcomes:
measure: Biochemical remission(serum levels of alanine aminotransferase, aspartate aminotransferase and Total bilirubin within normal ranges)
timeFrame: 12 months
measure: immunology remission(=serum levels of T cell subsets, immune globulin, and complement within normal ranges) and lack of other side effects.
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of biochemical remission 2 times increase of serum levels of alanine aminotransferase, aspartate aminotransferase and Total bilirubin.
timeFrame: 12 months
measure: Suspected rejection detected by clinical feature or biopsy.
timeFrame: 12 months
measure: Incidence of 2 times increase of immunology related level(serum levels of T cell subsets,immune globulin) or present other side effects.
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Nanjing Medical University
name: Hong Wang, M.D.,PH.D.
role: STUDY_CHAIR
References:
citation: Chung YY, Rahim MN, Heneghan MA. Autoimmune hepatitis and pregnancy: considerations for the clinician. Expert Rev Clin Immunol. 2022 Apr;18(4):325-333. doi: 10.1080/1744666X.2022.2044307. Epub 2022 Mar 2.