Liver Transplant FailureNCT03815864
Antibodies and Liver Retransplantation
An observational study of Liver Transplant Failure and Antibody-mediated Rejection, run by London Health Sciences Centre.
Trial summary
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Liver Transplant Failure, Antibody-mediated Rejection
- What is being tested?
- Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 1977to 1 Jan 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: all patients who have undergone a repeat transplantation of the liver at LHSC.
Who may be able to join
- Recipients of a second liver transplantation performed at LHSC
Who cannot join
- Recipients of ABO incompatible second liver transplantation
- Recipients of multiple organs
About this study
Official title: 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
Read the 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.
- Being tested
- Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
- Keywords
- donor specific antibody, autoantibody, human leucocyte antigen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantationDiagnostic test
Also called AT1R antibody
Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation | |
| 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 Receives: Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retransplant graft survival
Average length of time the second liver graft remains in a living recipient regardless of function
Measured: 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 outcomes (1)
Patient survival
Average length of time a recipient is alive regardless of presence of the second liver transplant
Measured: From date of transplantation until the date of death from any cause assessed up to 240 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start1 Jan 1977
- Primary completion1 Jan 2021 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Liver Transplant FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vivian McAlister, London Health Sciences Centre
- Investigators
- Vivian McAlister, Principal investigator, London Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03815864
- Sponsor's protocol ID
- 106961
- Status last verified
- Jan 2019
- First submitted
- 20 Jan 2019
- Last updated
- 28 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.
Publications
Xu Q, McAlister VC, House AA, Molinari M, Leckie S, Zeevi A. Autoantibodies to LG3 are associated with poor long-term survival after liver retransplantation. Clin Transplant. 2021 Jul;35(7):e14318. doi: 10.1111/ctr.14318. Epub 2021 Apr 25.
PubMed 33871888Xu Q, McAlister VC, Leckie S, House AA, Skaro A, Marotta P. Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation. Am J Transplant. 2020 Jan;20(1):282-288. doi: 10.1111/ajt.15571. Epub 2019 Sep 6.
PubMed 31419065
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Donor Specific Antibodies, Other Anti-human Leucocyte Antibodies and Autoantibodies in the Outcome of Liver Retransplantation
- ClinicalTrials.gov ID
- NCT03815864
- Acronym / sponsor ID
- 106961
- Keywords
- donor specific antibody, autoantibody, human leucocyte antigen
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- London Health Sciences CentreUniversity, hospital or other
- Study start
- 1 Jan 1977 (actual)
- Primary completion
- 1 Jan 2021 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 24 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D2SA+ | – | Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantationMedian 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 |
| D2SA- | – | Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantationMedian 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- all patients who have undergone a repeat transplantation of the liver at LHSC.
Key inclusion criteria (1 listed)
- Recipients of a second liver transplantation performed at LHSC
Key exclusion criteria (2 listed)
- Recipients of ABO incompatible second liver transplantation
- Recipients of multiple organs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantationAlso: AT1R antibodyAnti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA) | Diagnostic test | D2SA+, D2SA- |
Primary outcome
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
1 secondary outcome
Patient survival
Time frame: From date of transplantation until the date of death from any cause assessed up to 240 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2019.
- Derived from this study: PubMed 33871888Xu Q, McAlister VC, House AA, Molinari M, Leckie S, Zeevi A. Autoantibodies to LG3 are associated with poor long-term survival after liver retransplantation. Clin Transplant. 2021 Jul;35(7):e14318. doi: 10.1111/ctr.14318. Epub 2021 Apr 25.
- Derived from this study: PubMed 31419065Xu Q, McAlister VC, Leckie S, House AA, Skaro A, Marotta P. Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation. Am J Transplant. 2020 Jan;20(1):282-288. doi: 10.1111/ajt.15571. Epub 2019 Sep 6.
- Individual participant dataSharing planned: Yes. Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vivian McAlister principal investigator
London Health Sciences Center
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Transplant Failure and Antibody-mediated Rejection, run by London Health Sciences Centre.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03815864, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2019.