A Cohort Study of Operationally Tolerant Allograft Recipients (ALLTOL)

August 25, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Prospective Cohort Study of Operationally Tolerant Allograft Recipients (ITN063ST)

Antirejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent their bodies from rejecting the new organ. Some organ transplant recipients can stop taking anti-rejection medicines without rejecting their transplanted organ (this is called 'tolerance'). The purpose of this study will collect samples and data from 'tolerant' liver or kidney transplant recipients in order to find out:

The purpose of this study is to collect samples and data in order to find out:

  • How long liver or kidney transplant recipients can remain tolerant;
  • What happens in the tolerant recipient's body over time; and
  • If there are patterns in the body that are linked to tolerance.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This is a multi-center, prospective, observational study in which operationally tolerant recipients of liver or kidney allografts will be followed longitudinally, with annual collections of clinical data and biological samples. All participants will be followed for the duration of the study, regardless of changes in their tolerance status.

Participants will be recruited by three main pathways:

  1. Tolerant participants from current and past Immune Tolerance Network (ITN) trials, including those who have already completed trial participation and those who are anticipated to complete trial participation,
  2. Tolerant participants referred by ITN affiliated investigators, academic and community transplant physicians and directly through outreach to transplant affinity groups such as the National Kidney Foundation (NKF), and
  3. Tolerant participants from the general transplant community who are reachable through general contact channels such as the ITN website, word-of-mouth referrals from existing participants, and social media.

Study Type

Observational

Enrollment (Actual)

41

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Georgia
      • Atlanta, Georgia, United States, 30324
        • Emory University School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Memorial Hospital of Chicago
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Medical Center
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburg of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Operationally tolerant recipients of liver or kidney allografts

Description

Inclusion Criteria:

  • Recipient of single organ liver or kidney allograft from a living or deceased donor;

  • At screening, operationally tolerant, as defined by:

    • Absence of any immunosuppressive therapy for ≥52 weeks prior to the screening visit, and
    • No evidence of allograft rejection in the 52 weeks prior to the screening visit, based on the allograft recipient's medical history.

  • Normal allograft function, defined as:

    • For liver transplant recipients: Liver function tests (ALT, GGT) both less than or equal to the upper limit of normal (ULN); and,
    • For kidney transplant recipients: Serum creatinine value corresponds to an estimated GFR > 45 ml/min/1.73 m^2.

  • Receiving regular follow-up for a kidney or liver transplant by a local physician:

    --Participants must be willing to allow the study team to contact and share medical information with this local physician.

  • Ability to sign informed consent.

Exclusion Criteria:

  • Current malignancy requiring recent surgery, ongoing chemotherapy, or radiation;
  • Transplant of another organ;
  • Current drug or alcohol dependency;
  • Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial; and
  • Inability to comply with the study visit schedule and required assessments.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Operationally Tolerant Kidney or Liver Allograft Recipients

Operational tolerance at baseline is defined as:

  • An absence of any immunosuppressive therapy for ≥ 52 weeks prior to the screening visit;
  • No evidence of allograft rejection in the 52 weeks prior to the screening visit (Day 0), based on the participant's medical history; and

  • Normal and stable allograft function at screening visit defined as-

    • For liver transplant recipients: Liver function tests (ALT, GGT) both less than or equal to the upper limit of normal (ULN)
    • For kidney transplant recipients: Serum creatinine value corresponds to an estimated glomerular filtration rate (GFR) > 45 ml/min/1.73 m^2.
Procedure: Blood Draw
Other Names:
  • Phlebotomy
  • Venipuncture
  • Venesection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Loss of Operational Tolerance
Time Frame: From operational tolerance to ITN063ST study completion, assessed up to 60 months
A participant is considered to have operational tolerance if they are off all immunosuppression medication while continuing to have stable allograft function and no rejection. For these participants, the date of operational tolerance is considered as 52 weeks from the participant's last documented dose of immunosuppression. A participant will be considered to have lost operational tolerance if they experience rejection, have loss of stable allograft function (in the absence of confounding factors), or restart immunosuppression. The endpoint was analyzed using Kaplan-Meier survival estimate and associated two-sided 95% confidence interval, using a delayed-entry model with left-truncation of survival times by censoring the time from achieving operational tolerance at the time of study enrollment. The survival estimate is at the time of the last of event.
From operational tolerance to ITN063ST study completion, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Development of Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA)
Time Frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)

Time to development of either:

  • de novo HLA antibodies (anti-HLA Ab) post-transplant. Alloantibody is defined as an antibody produced following the introduction of an alloantigen into the system of an individual lacking that particular antigen; OR
  • Donor Specific Antibodies (DSA), a newly developed alloantibody that is against the donor organ.

Alloantibodies are important mediators of acute and chronic rejection.

**These data are not yet available.**
Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)
Number of Participants With Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection
Time Frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)

Number of participants with acute rejection, steroid resistant rejection and/or chronic rejection.

Criteria employed for acute and chronic rejection: Banff guidelines.
Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)
Number of Participants With Graft Loss, Not Including Death With a Functioning Graft
Time Frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)
A participant is considered to have graft loss when the participant is retransplanted with another donor kidney, relisted for transplantation, or dies with a non-functioning graft.
Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

PPD
Rho Federal Systems Division, Inc.
Immune Tolerance Network (ITN)

Investigators

  • Study Chair: Sindhu Chandran, M.D., Immune Tolerance Network (ITN)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2016

Primary Completion (Actual)

March 24, 2020

Study Completion (Actual)

March 24, 2020

Study Registration Dates

First Submitted

April 6, 2016

First Submitted That Met QC Criteria

April 14, 2016

First Posted (Estimate)

April 19, 2016

Study Record Updates

Last Update Posted (Actual)

September 21, 2021

Last Update Submitted That Met QC Criteria

August 25, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • DAIT ITN063ST
  • UM1AI109565 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

IPD Sharing Time Frame

On average, within 24 months after database lock for the trial.

IPD Sharing Access Criteria

Open access.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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