Antibodies and Liver Retransplantation

January 24, 2019 updated by: Vivian McAlister, London Health Sciences Centre

Role of Donor Specific Antibodies, Other Anti-human Leucocyte Antibodies and Autoantibodies in the Outcome of Liver Retransplantation

Despite reports that associate donor specific antibody (DSA) with rejection after liver transplantation, grafts are still allocated according to blood group (ABO) but not human leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible clinical association between adverse recipient outcome and DSA. Re-transplantation provides a test environment where the presence of preformed DSA or other antibodies is prevalent and events (graft loss) more common so that the effect of these antibodies on outcome should be apparent. This is an observational study of routine clinical care to determine these effects on our own patients. The goal is to perfect donor-recipient matching to attain the best outcome. In addition, we may develop hypotheses and potential treatments that would be tested in further clinical trials

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Despite reports that associate donor specific antibody (DSA) with rejection after liver transplantation, grafts are still allocated according to blood group (ABO) but not human leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible clinical association between adverse recipient outcome and DSA. Re-transplantation provides a test environment where the presence of preformed DSA or other antibodies is prevalent and events (graft loss) more common so that the effect of these antibodies on outcome should be apparent. This is an observational study of routine clinical care to determine these effects on our own patients.

In phase 1, we will examine the effect of antibodies specifically directed against the second donor in liver retransplantation. Other factors known to effect the outcome will be checked to allow for risk adjustment.

In phase 2, we will examine the role played by specific auto-antibodies such as angiotensin II receptor type 1 antibodies and endothelin-1 type A receptor antibodies on the outcome of liver retransplantation.

The goal of these observational study is to perfect donor-recipient matching to attain the best outcome. In addition, we may develop hypotheses and potential treatments that would be tested in further clinical trials.

Study Type

Observational

Enrollment (Anticipated)

200

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

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

all patients who have undergone a repeat transplantation of the liver at LHSC.

Description

Inclusion Criteria:

  • Recipients of a second liver transplantation performed at LHSC

Exclusion Criteria:

  • Recipients of ABO incompatible second liver transplantation
  • Recipients of multiple organs

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
D2SA+
Median fluoresce intensity > or = 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
Diagnostic test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)
Other Names:
  • AT1R antibody
D2SA-
Median fluoresce intensity < 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
Diagnostic test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)
Other Names:
  • AT1R antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Retransplant graft survival
Time Frame: From date of transplantation until the date of next transplantation or date of death from any cause, whichever came first, assessed up to 240 months
Average length of time the second liver graft remains in a living recipient regardless of function
From date of transplantation until the date of next transplantation or date of death from any cause, whichever came first, assessed up to 240 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient survival
Time Frame: From date of transplantation until the date of death from any cause assessed up to 240 months
Average length of time a recipient is alive regardless of presence of the second liver transplant
From date of transplantation until the date of death from any cause assessed up to 240 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute rejection
Time Frame: From date of transplantation until the date of first documented acute rejection assessed up to 240 months
number of participants with a clinically diagnosed and treated episode of rejection (either acute cellular or humoral)
From date of transplantation until the date of first documented acute rejection assessed up to 240 months

Collaborators and Investigators

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

Sponsor

London Health Sciences Centre

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.

General Publications

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)

January 1, 1977

Primary Completion (ANTICIPATED)

January 1, 2021

Study Completion (ANTICIPATED)

January 1, 2026

Study Registration Dates

First Submitted

January 20, 2019

First Submitted That Met QC Criteria

January 22, 2019

First Posted (ACTUAL)

January 24, 2019

Study Record Updates

Last Update Posted (ACTUAL)

January 28, 2019

Last Update Submitted That Met QC Criteria

January 24, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 106961

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.

IPD Sharing Time Frame

From publication until 5 years later

IPD Sharing Access Criteria

De-identified subject level data will be shared with researchers who contact the principal investigator, submit a research plan and sign an agreement. Approval by Western Research Ethics may be required depending on the request.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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