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A Cohort Study of Operationally Tolerant Allograft Recipients (ALLTOL)

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ClinicalTrials.gov Identifier: NCT02743793
Recruitment Status : Terminated (COVID-19 pandemic and potential risks to study participants and study staff.)
First Posted : April 19, 2016
Last Update Posted : April 13, 2020
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date April 6, 2016
First Posted Date April 19, 2016
Last Update Posted Date April 13, 2020
Actual Study Start Date June 30, 2016
Actual Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 10, 2019)
Time to Loss of Operational Tolerance [ Time Frame: Day 0 to Year 5 ]
Operational tolerance (to their kidney or liver transplant) defined by:
  • Absence of rejection (biopsy-proven or clinical rejection), as determined by medical history;
  • Maintenance off immunosuppressive medication, except for short courses of steroids for non-allograft related conditions (i.e., asthma); and
  • Normal and stable allograft function:
    • For liver transplant recipients-Liver function tests (ALT, GGT) that have not increased more than 50% above the participant's baseline values; and
    • For kidney transplant recipients- Serum creatinine values that have not increased more than 25% above the participant's baseline values.
Original Primary Outcome Measures
 (submitted: April 14, 2016)
Kaplan-Meier Analysis of Time-to-Occurrence: Percentage of Participants with Loss of Operational Tolerance by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
Operational tolerance (to their kidney or liver transplant) defined by:
  • Absence of rejection, as determined by medical history;
  • Maintenance off immunosuppressive medication, with the exception of short courses of steroids for nonallograft related conditions; and
  • Normal and stable allograft function, defined respectively as liver function tests (ALT, GGT-for liver transplant recipients) or serum creatinine (for kidney transplant recipients) that have not increased more than 50% above the participant's baseline liver function test or serum creatinine value. The baseline value is the liver function tests or serum creatinine drawn at the screening (Day 0) visit.
Change History
Current Secondary Outcome Measures
 (submitted: October 10, 2019)
  • Time to Development of Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA) [ Time Frame: Day 0 to Year 5 ]
    Time to development of either:
    1. 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
    2. Donor Specific Antibodies (DSA), a newly developed alloantibody that is against the donor organ.
    Alloantibodies are important mediators of acute and chronic rejection.
  • Time to First Episode of Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection [ Time Frame: Day 0 to Year 5 ]
    Time to first episode of acute rejection, steroid resistant rejection and/or chronic rejection.
  • Time to Graft Loss [ Time Frame: Day 0 to Year 5 ]
    Time to graft loss, not including participant death with functioning graft.
Original Secondary Outcome Measures
 (submitted: April 14, 2016)
  • Kaplan-Meier Analysis of Time-to-Occurrence: Percentage of Participants that Develop de novo Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA) by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
  • Kaplan-Meier Analysis of Time-to-Occurrence:Percentage of Participants that Develop First Episode of Rejection by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
    First Episode of Acute Rejection, Steroid Resistant Rejection and Chronic Rejection
  • Kaplan-Meier Analysis of Time-to-Occurrence: Percentage of Participants that Experience Graft Loss by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
  • Kaplan-Meier Analysis of Time-to-Occurrence: Percentage of Participant Survival by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
    All-cause mortality, liver or kidney transplant recipients.
  • Changes in Renal Function Over Time in Renal Transplant Recipients by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
    Defined as estimated glomerular filtration rate (GFR) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
  • Changes in Liver Function Tests (LFTs) Over Time in Liver Transplant Recipients by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
    Serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT)
  • Kaplan-Meier Analysis of Time-to-Occurrence: Incidence of Biliary Complications in Liver Transplant Recipients by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
    Incidence of medical outcomes associated with long-term immunosuppression such as diabetes, hypertension, hyperlipidemia.
  • Incidence of Diabetes or Use of Concomitant Medications for Hypertension and/or Hyperlipidemia by Visit [ Time Frame: Day 0 and years 1,2,3,4, and 5 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title A Cohort Study of Operationally Tolerant Allograft Recipients
Official Title A Prospective Cohort Study of Operationally Tolerant Allograft Recipients (ITN063ST)
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.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood
Sampling Method Probability Sample
Study Population Operationally tolerant recipients of liver or kidney allografts
Condition
  • Kidney Transplant
  • Liver Transplant
Intervention Procedure: Blood Draw
Other Names:
  • Phlebotomy
  • Venesection
  • Venipuncture
Study Groups/Cohorts 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.
Intervention: Procedure: Blood Draw
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Terminated
Actual Enrollment
 (submitted: April 9, 2020)
41
Original Estimated Enrollment
 (submitted: April 14, 2016)
70
Actual Study Completion Date March 24, 2020
Actual Primary Completion Date March 24, 2020   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02743793
Other Study ID Numbers DAIT ITN063ST
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators Immune Tolerance Network (ITN)
Investigators
Study Chair: Sindhu Chandran, M.D. Immune Tolerance Network (ITN)
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date April 2020