Liver TransplantationDSATHNCT02556879
Immunization Anti HLA in the Liver Transplant Recipients (DSATH)
A study testing Donor specific antibodies, Serum bank and DNA bank in people with Liver Transplantation and Graft Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Anti HLA alloimmunization against the donor evaluated by the detection of anti-donor specific antibodies (DSA) is an underestimated factor in liver transplantation and may contribute to dysfunction and graft loss , especially among candidates for retransplantation, that have major immunization. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Transplantation, Graft Failure
- What is being tested?
- Donor specific antibodies, Serum bank and DNA bank
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 9 Mar 2016to Dec 2021
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years with no upper age limit,
- Candidate for a liver retransplantation, whatever the indication, the period or the number of retransplantation
- Recipient of a social protection scheme or entitled
- Signature of informed consent
Who cannot join
- HIV positive patient,
- Multi-organ transplantation.
Trial locations and contacts
1 site in 1 country.
France1 site
Unité Médicale de Transplantation Hépatique In Service d'Hépato-Gastro-Entérologie
Päris, 75013
About this study
Anti HLA alloimmunization against the donor evaluated by the detection of anti-donor specific antibodies (DSA) is an underestimated factor in liver transplantation and may contribute to dysfunction and graft loss , especially among candidates for retransplantation, that have major immunization.
This study will analyzed immunization markers at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions due to humoral immunization, to establish further investigations and to adapt early immunosuppressive therapy.
Read the detailed description
Humoral rejection, related to immunization of the patient against the graft, is diagnosed by the presence of DSA. This serious complication, responsible for dysfunction and graft loss in kidney and heart transplant, is treated by strengthening the immunosuppressive treatment. Humoral rejection is poorly characterized in liver transplantation, but might explain the severe dysfunctions and misunderstood losses of liver transplant. In a preliminary study after liver transplantation, it was observed that the presence of DSAs was more common among patients with unexplained dysfunction (n = 22) compared to patients without dysfunction (n = 69) (95% versus 51%). After liver transplantation, 20% of patients are immunized, against 50% after retransplantation, and after retransplantation, approximately 40% of patients present with graft dysfunction within 2 years.
The role of humoral rejection in graft lesion and loss is unknown after liver transplantation because DSAs are not evaluated and histological lesions associated with DSAs are not analyzed. It is essential to characterize the humoral rejection in liver transplantation or after liver retransplantation (highly immunized population) and immunization markers that are responsible, for early management of this complication by an increased immunosuppressive therapy as it is done for kidney and heart transplantation. This could limit the progression to graft loss.
A specific anti HLA immunization against the donor (DSA - Donor Specific Antibodies) is an underestimated factor in liver transplantation and may contribute to dysfunction and loss of liver graft, especially among candidates for retransplantation, stronger immune.
This study will look for these markers of immunization at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions, to establish further investigations and to adapt early immunosuppressive therapy.
Methodology, experimental design: prospective, multicenter study. Results of anti HLA antibodies and DSA will not be given not to influence the teams on patient treatment.
Inclusion in the pre-retransplantation visit : obtaining of the informed consent, HLA and anti-HLA antibodies, HLA Typing.
Visit before-ReTH: HLA antibodies and DSA Visit 1 (day of transplant): Standard biology, HLA antibodies and DSA, Crossmatch, Histological analysis of liver de-transplantation locally and centralized.
Visits 2 and 3 (months 1 and 3 post retransplantation) : Standard biology, anti-HLA antibodies and DSA, liver Doppler Ultrasound (as usual the center).
Visits 4 and 5 (months 12 and 24 post retransplantation), and in case of unexplained hepatic dysfunction: Standard biology, HLA antibodies and DSA, liver Doppler-Ultrasound, Fibroscan and hepatic puncture biopsy : histological analysis on site and centralized.
Number of subjects required: 100 patients to be included (200 patients eligible to be selected in pre-transplant consultation for 100 patients retransplanted to include).
Total study duration: up to 6 years (3 years for inclusion and 3 years of follow-up - up to 1 year pre waiting Reth and 2 years post-transplant) Inclusion period: 2 years Duration of participation for a patient: up to 3 years (1 year maximum pre retransplantation waiting + 2 years after transplantation)
Number of participating centers: 11
- Conditions
- Liver Transplantation, Graft Failure
- Being tested
- Donor specific antibodies, Serum bank, DNA bank, Liver biopsy, Liver ultrasounds and Fibroscan
- Keywords
- Liver transplantation, Graft failure, Donor specific antibodies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor specific antibodiesBiological
Additional samples for Donor specific antibodies at each visit
Serum bankBiological
Additional samples for serum bank at each visit if possible
DNA bankBiological
Additional sample for DNA bank at inclusion visit if possible
Liver biopsyProcedure or surgery
Liver biopsy at 12 and 24 months after retransplantation (depending the centers : procedure performed in routine or interventional procedure)
Liver ultrasounds and FibroscanProcedure or surgery
Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (depending the centers : procedure performed in routine or interventional procedure)
| Study group | Role | What they receive |
|---|---|---|
| Liver retransplantation | Other | * Donor specific antibodies :Additional samples for Donor specific at each visit
* Serum bank : Additional samples for serum bank at each visit if possible
* DNA banq : Additional sample for DNA banq at inclusion visit if possible
* Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure)
* Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure) Receives: Biological: Donor specific antibodies; Biological: Serum bank; Biological: DNA bank; Procedure: Liver biopsy; Procedure: Liver ultrasounds and Fibroscan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Risk of graft failure at 24 months (Odds Ratio) depending on the presence of DSA at retransplantation.
The graft failure is defined by abnormal hepatic tests (AST, ALT, GGT, PAL, total and conjugated bilirubin, PT, INR), and/or abnormal hepatic histology , and/or abnormal hepatic imagery.
Measured: 24 months after retransplantation
Secondary outcomes (5)
Evaluate the association between the presence of the DSA at retransplantation and histological abnormalities of the explant and graft. ( Pearson's chi-square test or Fischer exact test).
The DSA will be detected by a luminex technology and the positivity will be mesurated by the mean fluorescence intensity. Histological findings of the explant associated with anti HLA immunization will be described and clustered by the approach proposed by Lefaucheur et al (34), the analysis of C4d is conducted.
The histological abnormalities graft will be evaluated from biopsies performed at 12 and 24 months.
Measured: retransplantation, 12 and 24 months after retransplantation
Evaluate the association between the presence of the DSA at before retransplantation and biological abnormalities graft from the previous donor
Measured: 9 months, 6 months, 3 months Before transplantation
Evaluate the association between the presence of the DSA at retransplantation and biological abnormalities graft at 1, 3, 12 and 24 months.( Pearson's chi-square test or Fischer exact test).
The presence of abnormality will be determined from the AST, ALT, GGT, PAL, total and conjugated bilirubin, PT, INR.
Measured: 1, 3, 12 and 24 months after retransplantation
Evaluate the association between the presence of DSA and fibrosis Fibroscan measured at 12 and 24 months. (Student t-test or non parametric test).
Measured: 12 and 24 months after retransplantation
Evaluate the association between the number of acute rejection episodes and the presence of the DSA at retransplantation and their evolution (especially of recurrence).(Pearson's chi-square test or Fischer exact test).
Measured: 24 months after retransplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2015 (estimated)
- Study start9 Mar 2016
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- PERDIGAO Fabiano, PH, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02556879
- Sponsor's protocol ID
- P140315
- Acronym
- DSATH
- Status last verified
- Sep 2019
- First submitted
- 3 Aug 2015
- Last updated
- 2 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunization Anti HLA in the Liver Transplant Recipients (DSATH)
- ClinicalTrials.gov ID
- NCT02556879
- Acronym / sponsor ID
- DSATH / P140315
- Conditions
- Liver Transplantation, Graft Failure
- Keywords
- Liver transplantation, Graft failure, Donor specific antibodies
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 9 Mar 2016 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 22 Sep 2015 (estimated)
- 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.
Anti HLA alloimmunization against the donor evaluated by the detection of anti-donor specific antibodies (DSA) is an underestimated factor in liver transplantation and may contribute to dysfunction and graft loss , especially among candidates for retransplantation, that have major immunization.
This study will analyzed immunization markers at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions due to humoral immunization, to establish further investigations and to adapt early immunosuppressive therapy.
Detailed description
Humoral rejection, related to immunization of the patient against the graft, is diagnosed by the presence of DSA. This serious complication, responsible for dysfunction and graft loss in kidney and heart transplant, is treated by strengthening the immunosuppressive treatment. Humoral rejection is poorly characterized in liver transplantation, but might explain the severe dysfunctions and misunderstood losses of liver transplant. In a preliminary study after liver transplantation, it was observed that the presence of DSAs was more common among patients with unexplained dysfunction (n = 22) compared to patients without dysfunction (n = 69) (95% versus 51%). After liver transplantation, 20% of patients are immunized, against 50% after retransplantation, and after retransplantation, approximately 40% of patients present with graft dysfunction within 2 years.
The role of humoral rejection in graft lesion and loss is unknown after liver transplantation because DSAs are not evaluated and histological lesions associated with DSAs are not analyzed. It is essential to characterize the humoral rejection in liver transplantation or after liver retransplantation (highly immunized population) and immunization markers that are responsible, for early management of this complication by an increased immunosuppressive therapy as it is done for kidney and heart transplantation. This could limit the progression to graft loss.
A specific anti HLA immunization against the donor (DSA - Donor Specific Antibodies) is an underestimated factor in liver transplantation and may contribute to dysfunction and loss of liver graft, especially among candidates for retransplantation, stronger immune.
This study will look for these markers of immunization at the time of liver retransplantation and systematically in patients follow-up. This will allow to characterize the histological lesions, to establish further investigations and to adapt early immunosuppressive therapy.
Methodology, experimental design: prospective, multicenter study. Results of anti HLA antibodies and DSA will not be given not to influence the teams on patient treatment.
Inclusion in the pre-retransplantation visit : obtaining of the informed consent, HLA and anti-HLA antibodies, HLA Typing.
Visit before-ReTH: HLA antibodies and DSA Visit 1 (day of transplant): Standard biology, HLA antibodies and DSA, Crossmatch, Histological analysis of liver de-transplantation locally and centralized.
Visits 2 and 3 (months 1 and 3 post retransplantation) : Standard biology, anti-HLA antibodies and DSA, liver Doppler Ultrasound (as usual the center).
Visits 4 and 5 (months 12 and 24 post retransplantation), and in case of unexplained hepatic dysfunction: Standard biology, HLA antibodies and DSA, liver Doppler-Ultrasound, Fibroscan and hepatic puncture biopsy : histological analysis on site and centralized.
Number of subjects required: 100 patients to be included (200 patients eligible to be selected in pre-transplant consultation for 100 patients retransplanted to include).
Total study duration: up to 6 years (3 years for inclusion and 3 years of follow-up - up to 1 year pre waiting Reth and 2 years post-transplant) Inclusion period: 2 years Duration of participation for a patient: up to 3 years (1 year maximum pre retransplantation waiting + 2 years after transplantation)
Number of participating centers: 11
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Liver retransplantation | Other | Biological: Donor specific antibodies, Biological: Serum bank, Biological: DNA bank, Procedure: Liver biopsy, Procedure: Liver ultrasounds and Fibroscan* Donor specific antibodies :Additional samples for Donor specific at each visit * Serum bank : Additional samples for serum bank at each visit if possible * DNA banq : Additional sample for DNA banq at inclusion visit if possible * Liver biopsy :Liver biopsy at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure) * Liver ultrasounds and Fibroscan : Liver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (dependind the centers : procedure performed in routine or interventional procedure) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years with no upper age limit,
- Candidate for a liver retransplantation, whatever the indication, the period or the number of retransplantation
- Recipient of a social protection scheme or entitled
- Signature of informed consent
Key exclusion criteria (2 listed)
- HIV positive patient,
- Multi-organ transplantation.
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 |
|---|---|---|
| Donor specific antibodiesAdditional samples for Donor specific antibodies at each visit | Biological | Liver retransplantation |
| Serum bankAdditional samples for serum bank at each visit if possible | Biological | Liver retransplantation |
| DNA bankAdditional sample for DNA bank at inclusion visit if possible | Biological | Liver retransplantation |
| Liver biopsyLiver biopsy at 12 and 24 months after retransplantation (depending the centers : procedure performed in routine or interventional procedure) | Procedure or surgery | Liver retransplantation |
| Liver ultrasounds and FibroscanLiver ultrasounds and Fibroscan at 12 and 24 months after retransplantation (depending the centers : procedure performed in routine or interventional procedure) | Procedure or surgery | Liver retransplantation |
Primary outcome
Risk of graft failure at 24 months (Odds Ratio) depending on the presence of DSA at retransplantation.
Time frame: 24 months after retransplantation
The graft failure is defined by abnormal hepatic tests (AST, ALT, GGT, PAL, total and conjugated bilirubin, PT, INR), and/or abnormal hepatic histology , and/or abnormal hepatic imagery.
5 secondary outcomes
Evaluate the association between the presence of the DSA at retransplantation and histological abnormalities of the explant and graft. ( Pearson's chi-square test or Fischer exact test).
Time frame: retransplantation, 12 and 24 months after retransplantation
Evaluate the association between the presence of the DSA at before retransplantation and biological abnormalities graft from the previous donor
Time frame: 9 months, 6 months, 3 months Before transplantation
Evaluate the association between the presence of the DSA at retransplantation and biological abnormalities graft at 1, 3, 12 and 24 months.( Pearson's chi-square test or Fischer exact test).
Time frame: 1, 3, 12 and 24 months after retransplantation
Evaluate the association between the presence of DSA and fibrosis Fibroscan measured at 12 and 24 months. (Student t-test or non parametric test).
Time frame: 12 and 24 months after retransplantation
Evaluate the association between the number of acute rejection episodes and the presence of the DSA at retransplantation and their evolution (especially of recurrence).(Pearson's chi-square test or Fischer exact test).
Time frame: 24 months after retransplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2019.
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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.
PERDIGAO Fabiano, PH, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Donor specific antibodies, Serum bank and DNA bank in people with Liver Transplantation and Graft Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 4 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 2 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Risk of graft failure at 24 months (Odds Ratio) depending on the presence of DSA at retransplantation. (time frame: 24 months after retransplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Oct 2019.