De Novo Autoimmune HepatitisNCT02056054
De Novo Autoimmune Hepatitis in Pediatric Liver Transplantation
An observational study of De Novo Autoimmune Hepatitis, run by Yale University.
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. Read more about this study
- Who is it for?
- Ages 3 months and olderHealthy volunteers can take part
- Conditions the study is for
- De Novo Autoimmune Hepatitis
- What is being tested?
- Pediatric transplant subject with d-AIH, Pediatric transplant subject with acute rejection and Pediatric transplant subject with chronic rejection
- How many people
- 157 participants
- Where
- No sites listed yet
- Study dates
- 9 Sep 2013to 25 Nov 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Cohorts will be obtained from clinical settings and include pediatric and adult subjects. See eligibility criteria for detailed descriptions of the population.
Who may be able to join
- Pediatric Transplant Patients
- Is >3-months and <21 years of age and a recipient of a single organ liver transplant
- Has allograft dysfunction (an ALT and/or GGTP > 2 times the upper limit of normal) due to acute rejection without a prior diagnosis of d-AIH
- Has allograft dysfunction (an ALT and/or GGT > 2 times the upper limit of normal) due to chronic rejection without a prior diagnosis of d-AIH
- Has a diagnosis of d-AIH
- Healthy Pediatric Control Subjects (Enrolled at Yale)
Show all 13Show fewer
- Is ≥ 1-year and < 18-years of age
- Not on any immune modulators
- Not on steroid therapy
- Has no underlying chronic inflammatory condition
- Adult Control Subjects (Enrolled at Yale) Non-transplanted Adult patients with autoimmune hepatitis and chronic hepatitis C will also be enrolled.
- Non-transplanted adults "18 Years or > " with Autoimmune Hepatitis
- Non-transplanted adults "18 Years or > " with chronic hepatitis C who are treatment naive.
Who cannot join
- Pediatric Transplant Patients - Multi-visceral organ transplant recipient
- Healthy Pediatric Control Subjects (Enrolled at Yale)
- <1-year and > 18-years of age
- Has chronic inflammatory condition
- On immune modulators or steroids
- On chronic medication(s)
- Adult transplanted patients with d-AIH (enrolled at Yale)
- Transplanted Adults ≥21-years of age with a diagnosis of d-AIH
About this study
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.
Read the detailed 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.
- Conditions
- De Novo Autoimmune Hepatitis
- Being tested
- Pediatric transplant subject with d-AIH, Pediatric transplant subject with acute rejection, Pediatric transplant subject with chronic rejection, Adult non-transplant patients with auto-immune hepatitis, Adult non-transplant subjects with chronic hepatitis C virus
- Keywords
- Autoimmune hepatitis, Liver transplantation, Hepatitis C
- Medical subject headings
- Hepatitis, Autoimmune, Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pediatric transplant subject with d-AIHOther
30 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws will depend on the patient's pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8.
Pediatric transplant subject with acute rejectionOther
Recipients with acute rejection will have blood drawn at time of diagnosis before treatment for rejection is instituted.
Pediatric transplant subject with chronic rejectionOther
Recipients with chronic rejection will have blood drawn either at diagnosis before treatment is instituted or for those with ongoing chronic rejection at the time of enrollment.
Adult non-transplant patients with auto-immune hepatitisOther
75 ml of blood will be collected during periods of disease quiescence and activity in non transplanted subjects with AIH who are enrolled. Research blood draws will be drawn along with clinical blood draws.
The exact number of blood draws for each subject will depend on his or her pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8.
Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed.
In the event that any enrolled subject undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media.
Adult non-transplant subjects with chronic hepatitis C virusOther
For enrolled patients with chronic hepatitis C, 75 ml of blood will be collected before the start of treatment. This will be a onetime blood draw prior to treatment. Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed.
In the event that any enrolled patient undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media.
Pediatric control subjectsOther
2 tablespoons of blood (30 ml) will be collected at each blood draw over a 2-year period. . The maximum amount of blood draws will be 3 however there will be no more than 1 blood draw within an 8-week period.
Adult transplanted subjects with de novo autoimmune hepatitisOther
75 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws for each subject will depend on his or her pattern of disease activity. However, no more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2-year study period will be 8.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with d-AIH | Pediatric transplant patients with de novo autoimmune hepatitis (d-AIH) will be enrolled at an outside center. Receives: Other: Pediatric transplant subject with d-AIH | |
| Subjects with Acute Rejection | Pediatric transplant patients with acute rejection will be enrolled at an outside center. Receives: Other: Pediatric transplant subject with acute rejection | |
| Subjects with Chronic Rejection | Pediatric transplant patients with chronic rejection will be enrolled at an outside center. Receives: Other: Pediatric transplant subject with chronic rejection | |
| Control Subjects | Healthy pediatric patients will be enrolled at the coordinating center (Yale). Receives: Other: Pediatric control subjects | |
| Subjects with Auto-immune Hepatitis | Adult non-transplant patients with auto-immune hepatitis will be enrolled at the coordinating center (Yale). Receives: Other: Adult non-transplant patients with auto-immune hepatitis | |
| Subjects with Chronic Hepatitis C Virus | Adult non-transplant patients with chronic hepatitis C will be enrolled at the coordinating center (Yale). Receives: Other: Adult non-transplant subjects with chronic hepatitis C virus | |
| Adult Subjects with d-AIH | Adult transplanted patients with de novo autoimmune hepatitis will be enrolled at the coordinating center (Yale). Receives: Other: Adult transplanted subjects with de novo autoimmune hepatitis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver Allograft Loss
Assessment to determine the frequency of liver allograft loss.
Measured: 3 years
Need for Transplantation
Assessment to determine the need for re-transplantation.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2014 (estimated)
- Study start9 Sep 2013
- Primary completion25 Nov 2019
- Study completion25 Nov 2019
Why it stopped: Study PI has moved institutions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for De Novo Autoimmune HepatitisStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Udeme Ekong, MD, MPH, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02056054
- Sponsor's protocol ID
- 1302011561
- Status last verified
- Dec 2021
- First submitted
- 28 Jan 2014
- Last updated
- 10 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- De Novo Autoimmune Hepatitis in Pediatric Liver Transplantation
- ClinicalTrials.gov ID
- NCT02056054
- Acronym / sponsor ID
- 1302011561
- Conditions
- De Novo Autoimmune Hepatitis
- Keywords
- Autoimmune hepatitis, Liver transplantation, Hepatitis C
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Study PI has moved institutions
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 9 Sep 2013 (actual)
- Primary completion
- 25 Nov 2019 (actual)
- Study completion
- 25 Nov 2019 (actual)
- First posted
- 5 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Subjects with d-AIH | – | Other: Pediatric transplant subject with d-AIHPediatric transplant patients with de novo autoimmune hepatitis (d-AIH) will be enrolled at an outside center. |
| Subjects with Acute Rejection | – | Other: Pediatric transplant subject with acute rejectionPediatric transplant patients with acute rejection will be enrolled at an outside center. |
| Subjects with Chronic Rejection | – | Other: Pediatric transplant subject with chronic rejectionPediatric transplant patients with chronic rejection will be enrolled at an outside center. |
| Control Subjects | – | Other: Pediatric control subjectsHealthy pediatric patients will be enrolled at the coordinating center (Yale). |
| Subjects with Auto-immune Hepatitis | – | Other: Adult non-transplant patients with auto-immune hepatitisAdult non-transplant patients with auto-immune hepatitis will be enrolled at the coordinating center (Yale). |
| Subjects with Chronic Hepatitis C Virus | – | Other: Adult non-transplant subjects with chronic hepatitis C virusAdult non-transplant patients with chronic hepatitis C will be enrolled at the coordinating center (Yale). |
| Adult Subjects with d-AIH | – | Other: Adult transplanted subjects with de novo autoimmune hepatitisAdult transplanted patients with de novo autoimmune hepatitis will be enrolled at the coordinating center (Yale). |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Cohorts will be obtained from clinical settings and include pediatric and adult subjects. See eligibility criteria for detailed descriptions of the population.
Key inclusion criteria (13 listed)
- Pediatric Transplant Patients
- Is >3-months and <21 years of age and a recipient of a single organ liver transplant
- Has allograft dysfunction (an ALT and/or GGTP > 2 times the upper limit of normal) due to acute rejection without a prior diagnosis of d-AIH
- Has allograft dysfunction (an ALT and/or GGT > 2 times the upper limit of normal) due to chronic rejection without a prior diagnosis of d-AIH
- Has a diagnosis of d-AIH
Key exclusion criteria (8 listed)
- Pediatric Transplant Patients - Multi-visceral organ transplant recipient
- Healthy Pediatric Control Subjects (Enrolled at Yale)
- <1-year and > 18-years of age
- Has chronic inflammatory condition
- On immune modulators or steroids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pediatric transplant subject with d-AIH30 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws will depend on the patient's pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8. | Other | Subjects with d-AIH |
| Pediatric transplant subject with acute rejectionRecipients with acute rejection will have blood drawn at time of diagnosis before treatment for rejection is instituted. | Other | Subjects with Acute Rejection |
| Pediatric transplant subject with chronic rejectionRecipients with chronic rejection will have blood drawn either at diagnosis before treatment is instituted or for those with ongoing chronic rejection at the time of enrollment. | Other | Subjects with Chronic Rejection |
| Adult non-transplant patients with auto-immune hepatitis75 ml of blood will be collected during periods of disease quiescence and activity in non transplanted subjects with AIH who are enrolled. Research blood draws will be drawn along with clinical blood draws. The exact number of blood draws for each subject will depend on his or her pattern of disease activity. No more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2 year study period will be 8. Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed. In the event that any enrolled subject undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media. | Other | Subjects with Auto-immune Hepatitis |
| Adult non-transplant subjects with chronic hepatitis C virusFor enrolled patients with chronic hepatitis C, 75 ml of blood will be collected before the start of treatment. This will be a onetime blood draw prior to treatment. Liver tissue (2 mm) will be obtained at the time a clinically indicated liver biopsy is performed. In the event that any enrolled patient undergoes liver transplantation, a portion of the explanted liver will be obtained and stored in special media. | Other | Subjects with Chronic Hepatitis C Virus |
| Pediatric control subjects2 tablespoons of blood (30 ml) will be collected at each blood draw over a 2-year period. . The maximum amount of blood draws will be 3 however there will be no more than 1 blood draw within an 8-week period. | Other | Control Subjects |
| Adult transplanted subjects with de novo autoimmune hepatitis75 ml of blood will be collected during periods of disease quiescence and activity in recipients with d-AIH who are enrolled. The exact number of blood draws for each subject will depend on his or her pattern of disease activity. However, no more than one blood draw will take place during an 8-week period. The maximum amount of blood draws over the 2-year study period will be 8. | Other | Adult Subjects with d-AIH |
Primary outcome
Liver Allograft Loss
Time frame: 3 years
Assessment to determine the frequency of liver allograft loss.
Need for Transplantation
Time frame: 3 years
Assessment to determine the need for re-transplantation.
Results and safety
The study was stopped early (reason given: Study PI has moved institutions). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2021.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Udeme Ekong, MD, MPH principal investigator
Yale University
Questions about this trial
What is this clinical trial studying?
An observational study of De Novo Autoimmune Hepatitis, run by Yale University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Study PI has moved institutions). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver Allograft Loss (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2021.