Transplant Surgery »  Research »  Clinical Research »  Clinical Trials »  OPTIMAL

Evaluation of Donor Specific Immune Senescence and Exhaustion as Biomarkers of Tolerance Post Liver Transplantation

Official Title:

Evaluation of Donor Specific Immune Senescence and Exhaustion as Biomarkers of Operational Tolerance Following Liver Transplantation in Adults (ITN056ST)

Basic Trial Information

Phase Type Age Sponsor Protocol IDs Status
Phase 2 Interventional 18 Years and older National Institute of Allergy and Infectious Diseases (NIAID) DAIT ITN056ST
NCT02533180
Enrolling patients

Study Design:


Principal Investigator

Professor of Surgery
Division of Transplant Surgery
Director, Abdominal Transplant Fellowship Program

Clinical Research Coordinator

UCSF Medical Center at Parnassus
(415) 476-2574 Phone

Trial Summary

The primary aim of this study is to determine whether a peripheral blood or graft lymphocyte phenotype of immune senescence or exhaustion is different between operationally tolerant and non-tolerant liver allograft recipients.

Eligibility

Inclusion Criteria:
Recipient participants must meet all of the following criteria to be eligible for this
study:

     1. At the time of screening:
    - 18 to 50 years old and more than 6 years post-transplant OR
    - Greater than 50 years old and more than 3 years post-transplant
     2. Recipient of either deceased or living donor liver transplant. Recipients of living
         donor transplants must have a donor who is also willing to enroll.
     3. Recipient of single organ transplant only
     4. Must have a screening liver biopsy that fulfills the following criteria based on the
         central pathology reading:
    - Portal inflammation and interface activity is preferably absent, but minimal to
       focal mild portal mononuclear inflammation may be present. Interface
       necro-inflammatory activity is absent or equivocal/minimal and, if present,
       involves a minority of portal tracts and not generally associated with fibrosis.
    - Negative for perivenular inflammation.
    - Lymphocytic bile duct damage, ductopenia, and biliary epithelial senescence
       changes are absent unless there is an alternative, non-immunological explanation
       (e.g. biliary strictures).
    - Fibrosis (if present) should be mild overall, and portal-to-portal bridging
       should not be more than rare. Perivenular and peri-sinusoidal fibrosis should
       not be more than mild according to the Banff criteria.
    - Findings for obliterative or foam cell arteriopathy are negative.
     5. Liver function tests (Direct bilirubin, alanine aminotransferase (ALT)), less than
         twice the upper limit of normal (ULN). ULN values for liver function tests will be
         defined by ranges from Harrison's Principles of Internal Medicine, 18th edition.
     6. Receiving calcineurin inhibitor (CNI) based maintenance immunosuppression.
         Participants may also concurrently receive:
    - Low dose mycophenolate mofetil (MMF ≤ 1500 mg daily) or mycophenolic acid (≤
       1080 mg daily), OR
    - Prednisone ≤ 7.5 mg daily, or equivalent corticosteroid..
     7. Ability to sign informed consent
Living donor participants must meet all of the following criteria to be eligible for this
study:

     1. At the time of screening: ≥18 years old
     2. Living donor of the liver allograft of an enrolled recipient participant
     3. Ability to sign informed consent
     4. Willingness to donate appropriate biologic samples
Exclusion Criteria:
Recipient participants who meet any of the following criteria will not be eligible for
this study:

     1. History of hepatitis C virus (HCV) infection (defined as a positive HCV antibody
         test).
     2. Positive antigen-antibody immunoassay for human immunodeficiency virus, HIV-1/2.
     3. Serum positivity for HBV surface antigen or HBV-DNA.
     4. History of immune-mediated liver disease in which immunosuppression discontinuation
         is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary
         cirrhosis).
     5. Any medical condition associated with a likely need for systemic corticosteroid
         administration, e.g., reactive airways disease.
     6. Prospective baseline liver biopsy showing any of the following: (see recipient
         inclusion criteria #4)
    - acute rejection according to the Banff global assessment criteria;
    - early or late chronic rejection according to the Banff global assessment
       criteria
    - inflammatory activity and/or fibrosis in excess of permissive criteria according
       to Banff 2012 criteria;
    - any other histological findings that might make participation in the trial
       unsafe. Eligibility will be determined by the findings on the central biopsy
       reading.
     7. Rejection within the 52 weeks prior to screening.
     8. Estimated glomerular filtration rate (GFR) <40 ml/min as calculated by CKD-EPI method
         (to mitigate the risk of worsening renal failure should rejection occur and high
         level of CNI be required).
     9. The need for chronic anti-coagulation that cannot be safely discontinued for a
         minimum of 1 week to safely perform a liver biopsy.
     10. Pregnant females and females of childbearing age who are not using an effective
         method of birth control.
     11. Current drug or alcohol dependency.
     12. Inability to comply with the study visit schedule and required assessments, including
         frequent liver function monitoring and protocol biopsies.
     13. Inability to comply with study directed treatment.
     14. Any medical condition that in the opinion of the principal investigator would
         interfere with safe completion of the trial.
     15. Participation in another interventional clinical trial within the 4 weeks prior to
         screening.
Living donor participants who meet any of the following criteria will not be eligible for
this study:
1. Any medical condition, such as anemia, coagulopathy, etc., that in the opinion of the
principal investigator would interfere with safe participation in the trial.

Detailed Description

People who have liver transplants must take anti-rejection medication (immunosuppression)
for the rest of their lives. If they stop, their immune system may reject the transplanted
liver. All anti-rejection medications have side effects. Because of the side effects of
anti-rejection medications, an important goal of transplant research is to allow people to
accept their transplanted organ without long term use of anti-rejection medications. This is
called tolerance. In this study, participants who received a liver transplant will have
their anti-rejection medication(s) gradually reduced over a period of time and then stopped.
The study calls this 'immunosuppression withdrawal'.
The purpose of this research study is to see how many people will develop tolerance after
immunosuppression withdrawal. The researchers also want to find out if there are blood or
liver biopsy tests that can help transplant doctors in the future predict whether it is safe
to decrease or stop anti-rejection medications in people who received a liver transplant.

Important

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

Information about this trial was obtained from the NIH Clinical Trials website, http://clinicaltrials.gov on 1/26/2017. UCSF specific information including the PI (Principal Investigator), trial enrollment status, and UCSF Study ID, supplement the ClinicalTrials.gov study posting.
X