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A Cohort Study of Operationally Tolerant Allograft Recipients (ALLTOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02743793
Recruitment Status : Terminated (COVID-19 pandemic and potential risks to study participants and study staff.)
First Posted : April 19, 2016
Results First Posted : September 21, 2021
Last Update Posted : September 21, 2021
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
PPD
Rho Federal Systems Division, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

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.

Condition or disease Intervention/treatment
Kidney Transplant Liver Transplant Procedure: Blood Draw

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.

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Study Type : Observational
Actual Enrollment : 41 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Cohort Study of Operationally Tolerant Allograft Recipients (ITN063ST)
Actual Study Start Date : June 30, 2016
Actual Primary Completion Date : March 24, 2020
Actual Study Completion Date : March 24, 2020

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
  • Venesection
  • Venipuncture




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.**


  2. 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.


  3. 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.


Biospecimen Retention:   Samples With DNA
Blood


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Operationally tolerant recipients of liver or kidney allografts
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743793


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30324
United States, Illinois
Ann & Robert H. Lurie Children's Memorial Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Pennsylvania
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburg of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
PPD
Rho Federal Systems Division, Inc.
Investigators
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Study Chair: Sindhu Chandran, M.D. Immune Tolerance Network (ITN)
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
Study Protocol  [PDF] September 4, 2019
Statistical Analysis Plan  [PDF] July 17, 2020

Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02743793    
Other Study ID Numbers: DAIT ITN063ST
UM1AI109565 ( U.S. NIH Grant/Contract )
First Posted: April 19, 2016    Key Record Dates
Results First Posted: September 21, 2021
Last Update Posted: September 21, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Time Frame: On average, within 24 months after database lock for the trial.
Access Criteria: Open access.
URL: https://www.immport.org/home
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
single organ liver or kidney allograft
operationally tolerant allograft recipients
longitudinal follow-up