Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT02056054 |
| Other study ID # |
1302011561 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 9, 2013 |
| Est. completion date |
November 25, 2019 |
Study information
| Verified date |
December 2021 |
| Source |
Yale University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to provide insights into the cause, development and effects of
de novo autoimmune hepatitis so that prevention and treatment strategies can be developed in
order to reduce post-liver transplant morbidity, the frequency of liver allograft loss and
the need for re-transplantation.
Description:
This is a multi-site study with Yale University as the coordinating site. Our research plan
is as follows:
Aim 1: To conduct a refined phenotypical and functional analysis of regulatory T cells in
study and control patient groups.
Rationale: We would like to extend our preliminary data observations in a larger patient
group and use this extended data set to conduct a refined phenotypical and functional
analysis of regulatory T cells in order to explore if the regulatory T cell phenotype and
function in d-AIH differs: (A) from that in controls defined as (i) non-transplanted patients
with autoimmune hepatitis (AIH), (ii) LT recipients with acute rejection, (iii) LT recipients
with chronic rejection, (iv) non-transplanted patients with chronic hepatitis C; (B)
according to the disease etiology leading to transplantation; (C) according to
immunosuppressive regimen prior to diagnosis of d-AIH being made and (D) over time during the
disease course. This could potentially give us some insight into the causes for immune
tolerance breakdown in d-AIH.
Aim 2: To investigate how over expression of IL-17A and HDAC9 genes relates to the regulatory
T cell defect observed in liver transplant recipients with d-AIH.
Rationale: Histone/protein deacetylases regulate chromatin remodeling, gene expression and
the functions of many transcription factors. Acetylation of histones leads to an open
chromatin structure permissive for the initiation of gene transcription and expression.
Histone deacetylase inhibition by Trichostatin-A (TSA) has been demonstrated to prevent the
production of IL-17A and sustain Foxp3 expression in human T-regs. Importantly, if
differentiation of T-regs into a Th17-like phenotype can be inhibited by TSA in d-AIH, this
might be of interest for the development of new therapeutic modalities.
We would like to first of all confirm our preliminary data observations in a larger patient
population and address any concerns about RNA integrity in formalin fixed paraffin embedded
tissue by using fresh liver biopsy tissue to assess the expression of genes involved in
T-cell anergy and immune tolerance in LT recipients.
