Kidney Transplant, Liver Transplant
Conditions
Keywords
single organ liver or kidney allograft, operationally tolerant allograft recipients, longitudinal follow-up
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
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.
Interventions
PROCEDUREBlood Draw
Sponsors
Immune Tolerance Network (ITN)
PPD Development, LP
Rho Federal Systems Division, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Loss of Operational Tolerance | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Development of Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA) | 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.\*\* |
| Number of Participants With Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection | 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. |
| Number of Participants With Graft Loss, Not Including Death With a Functioning Graft | 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. |
Countries
United States
Participant flow
Recruitment details
41 tolerant kidney and liver participants were recruited from June 2016 through February 2020 along three main pathways 1) from current and past Immune Tolerance Network (ITN) trials, 2) by ITN affiliation investigators, academic community transplant physicians, and through outreach to transplant affinity groups, and 3) from the general transplant community through media channels.
Pre-assignment details
Informed consent was obtained from potentially eligible individuals who underwent a screening visit to determine eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled, Not Eligible These participants were consented and enrolled into the study, but did not meet eligibility criteria. | 5 |
| Accrued These participations met all eligibility criteria and completed at least one mechanistic sample collection. | 36 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | No Primary Care Physician | 0 | 1 |
| Overall Study | Screen Failure | 4 | 0 |
| Overall Study | Study stopped due to COVID-19 pandemic | 0 | 32 |
| Overall Study | Travel/remote visits could not be performed at nursing facility | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Enrolled, Not Eligible | Accrued | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 9 Participants | 11 Participants |
| Age, Categorical >=65 years | 2 Participants | 6 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 21 Participants | 22 Participants |
| Age, Continuous | 39 Years STANDARD_DEVIATION 29.4 | 40 Years STANDARD_DEVIATION 24.3 | 40 Years STANDARD_DEVIATION 24.5 |
| Alanine aminotransferase (ALT) | 68.0 U/L | 24.5 U/L STANDARD_DEVIATION 11.98 | 26.1 U/L STANDARD_DEVIATION 14.42 |
| Creatinine | 2.6 mg/dL | 1.3 mg/dL STANDARD_DEVIATION 0.48 | 1.4 mg/dL STANDARD_DEVIATION 0.6 |
| Duration of operational tolerance at time of enrollment. | 7.6 years STANDARD_DEVIATION 5.07 | 8.1 years STANDARD_DEVIATION 7.53 | 8.1 years STANDARD_DEVIATION 7.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 36 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gamma glutamyltransferase (GGT) | 18 U/L | 32.4 U/L STANDARD_DEVIATION 49.33 | 31.8 U/L STANDARD_DEVIATION 48.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 33 Participants | 38 Participants |
| Region of Enrollment United States | 5 participants | 36 participants | 41 participants |
| Sex: Female, Male Female | 0 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 5 | 1 / 36 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 36 |
Outcome results
Primary
Time to Loss of Operational Tolerance
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.
Time frame: From operational tolerance to ITN063ST study completion, assessed up to 60 months
Population: Participants who met all eligibility criteria and completed at least one mechanistic sample collection.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Accrued | Time to Loss of Operational Tolerance | 6.6 Years to loss of operational tolerance | Standard Deviation 5.38 |
95% CI: [21.3, 87.9]
Secondary
Number of Participants With Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection
Number of participants with acute rejection, steroid resistant rejection and/or chronic rejection. Criteria employed for acute and chronic rejection: Banff guidelines.
Time frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)
Population: Participants who met all eligibility criteria and completed at least one mechanistic sample collection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Accrued | Number of Participants With Biopsy-Proven or Clinical Acute Rejection, Steroid Resistant Rejection and/or Chronic Rejection | 0 Participants |
Secondary
Number of Participants With Graft Loss, Not Including Death With a Functioning Graft
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.
Time frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)
Population: Participants who met all eligibility criteria and completed at least one mechanistic sample collection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Accrued | Number of Participants With Graft Loss, Not Including Death With a Functioning Graft | 0 Participants |
Secondary
Time to Development of Anti-Human Leukocyte Antigen (HLA) Antibody or Donor Specific Antibodies (DSA)
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.\*\*
Time frame: Day 0 (Study Enrollment) to Study Completion (Up to 3.7 years)