Renal TransplantationMICROMARK RJNCT03098238
Endothelial Microparticules and Antibody Mediated Rejection and Kidney Transplantation: Biomarker of Antibody-mediated Rejection in Kidney Transplantation
A study testing Biological sample in people with Renal Transplantation, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Context and rationale: Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), leading to graft failure. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Renal Transplantation
- What is being tested?
- Biological sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 249 participants
- Where
- 1 siteFrance
- Study dates
- 30 Nov 2017to 4 Jun 2020
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 18 years at time of inclusion
- Renal transplant patients monitored at Montpellier University Hospital
- With a recent or planned realization of a graft biopsy
- Patients with DSA (s) detected by Single Antigen Bead Assay (SAB, LabScreen Single Antigen, One Lambda Kit) with an average fluorescence intensity> 500 IU Or Patients without DSA transplanted to a year with a systematic biopsy aspiration.
Who cannot join
- Refusal to participate in or to undergo the examination
- Major protected by guardianship
- History of treated humoral rejection
- Incompatible graft ABO
- Multi-organ transplantation
- Cardiovascular disease active (myocardial infarction <3 months, arteriopathy obliterating lower limbs stage III or IV)
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- Sepsis in progress
- Evolving Cancers
- Lupus nephropathy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Endothelial Microparticules as Biomarker of Antibody-mediated Rejection in Kidney Transplantation
Context and rationale:
Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), leading to graft failure.
Read more
The main difficulty to manage the humoral rejection is the delay of the diagnosis and the treatment to slow the evolution towards fibrosis.
Positivity of anti-HLA antibodies is the main risk factor for the rejection but the only way to make the diagnosis of humoral rejection is to perform a graft biopsy, an invasive process.
Endothelial microparticles (MPE) are small membrane vesicles generated by endothelial cell activation and / or apoptosis processes.
We test the hypothesis that endothelial microparticles are an early diagnostic biomarker of humoral rejection in renal transplantation allowing to detect it at the "subclinical" stage.
Primary and secondary objectives:
The main objective of this study is to estimate the performance of MPE plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA. The secondary objective is to investigate by mass spectrometry the MPEs specific to the endothelium of the graft and to evaluate their diagnostic performance in relation to non-specific MEPs
Methodology :
We will conduct a cross-sectional evaluation of a diagnostic method from a collection of biological samples. The gold standard for the diagnosis of humoral rejection is the histological diagnosis on graft biopsy. The new test under study will be the flow cytometric assay of the MPE concentration carried out on plasma taken on the day of the graft biopsy.
Feasibility:
Among the active list of renal transplant patients attending the Montpellier University Hospital, we estimate that we can include the number of subjects required (N = 250) over 18 months. This work will be carried out in a laboratory with all the tools and techniques used, in particular flow cytometry and mass spectrometry, perfectly mastered and realized on dedicated technical platforms
Benefits / Outlook:
find a non-invasive early diagnostic biomarker to detect humoral rejection from the "subclinical" stage in order to set up an adapted treatment as quickly as possible.
Read the detailed description
Context and rationale:
Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), the binding of which can activate the renal endothelium and be responsible for inflammation leading to fibrosis and graft destruction.
The main obstacle in the management of the humoral rejection is the delay of the diagnosis and the treatment to slow the evolution towards fibrosis. At the beginning of the process there is no "apparent" dysfunction of the graft (elevation of serum creatinine and / or proteinuria) but only inflammation of the renal parenchyma: this is referred to as "subclinical" humoral rejection. Graft dysfunction occurs only when the inflammation is serious and responsible for irreversible lesions of fibrosis.
New sensitive detection techniques for anti-HLA antibodies allow to detect DSA well before the onset of humoral rejection but the only way to make the diagnosis of humoral rejection is to perform a graft biopsy, an invasive process with a hemorrhagic risk which can not be repeated too frequently.
Endothelial microparticles (MPE) are small membrane vesicles generated by endothelial cell activation and / or apoptosis processes. An increasing level in circulating blood appears today as a endothelial dysfunction in many pathologies. Their role in humoral rejection, a model of endothelial dysfunction, has never been explored.
We wish to test the hypothesis that endothelial microparticles are an early diagnostic biomarker of humoral rejection in renal transplantation allowing to detect it at the "subclinical" stage.
Primary and secondary objectives:
The main objective of this study is to estimate the performance of MPE plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA. The secondary objective is to investigate by mass spectrometry the MPEs specific to the endothelium of the graft and to evaluate their diagnostic performance in relation to non-specific MEPs
Methodology :
We will conduct a cross-sectional evaluation of a diagnostic method from a collection of biological samples. The gold standard for the diagnosis of humoral rejection is the histological diagnosis on graft biopsy. The new test under study will be the flow cytometric assay of the MPE concentration carried out on plasma taken on the day of the graft biopsy.
Feasibility:
Among the active list of renal transplant patients attending the Montpellier University Hospital, we estimate that we can include the number of subjects required (N = 250) over 18 months. This work will be carried out in a laboratory with all the tools and techniques used, in particular flow cytometry and mass spectrometry, perfectly mastered and realized on dedicated technical platforms
Benefits / Outlook:
At a time when the shortage of organs is growing and becomes a real public health problem, it becomes essential to better control the management of humoral rejection, the main cause of long-term renal graft loss. One of the key steps in this step is to find a non-invasive early diagnostic biomarker to detect humoral rejection from the "subclinical" stage in order to set up an adapted treatment as quickly as possible.
- Conditions
- Renal Transplantation
- Being tested
- Biological sample
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological sampleBiological
Biological sampling of two citrate tubes (18 ml) during a normal blood
| Study group | Role | What they receive |
|---|---|---|
| Patients without humoral rejection or DSA | Other | Renal transplant patients with systematic kidney biopsy at 3 months and 12 months Patients without humoral rejection or DSA (Donor Specific Antibodies) Receives: Biological: Biological sample |
| Patient without humoral rejection with a DSA | Other | Patient without humoral rejection with a DSA (Donor Specific Antibodies)Patients with a graft biopsy for a donor-specific anti-HLA antibody Receives: Biological: Biological sample |
| Patients with humoral rejection | Other | Patients with humoral rejection Receives: Biological: Biological sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of endothelial microparticles
Endothelial microparticle (MPE) plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA.
Measured: 1 day
Secondary outcomes (1)
Presence of specific MEPs
Presence of MPEs specific to the graft endothelium and to evaluate their diagnostic performance in relation to non-specific MEPs
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start30 Nov 2017
- Primary completion4 Jun 2020
- Study completion4 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Moglie LE QUINTREC DONNETTE, Study director, University Hospital, Montpellier
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098238
- Sponsor's protocol ID
- RECHMPL16_0263
- Other IDs
- UF 9746
- Acronym
- MICROMARK RJ
- Status last verified
- Jan 2020
- First submitted
- 26 Mar 2017
- Last updated
- 14 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: NC
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endothelial Microparticules as Biomarker of Antibody-mediated Rejection in Kidney Transplantation
- ClinicalTrials.gov ID
- NCT03098238
- Acronym / sponsor ID
- MICROMARK RJ / RECHMPL16_0263
- Conditions
- Renal Transplantation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 4 Jun 2020 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 31 Mar 2017 (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.
Context and rationale:
Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), leading to graft failure.
The main difficulty to manage the humoral rejection is the delay of the diagnosis and the treatment to slow the evolution towards fibrosis.
Positivity of anti-HLA antibodies is the main risk factor for the rejection but the only way to make the diagnosis of humoral rejection is to perform a graft biopsy, an invasive process.
Endothelial microparticles (MPE) are small membrane vesicles generated by endothelial cell activation and / or apoptosis processes.
We test the hypothesis that endothelial microparticles are an early diagnostic biomarker of humoral rejection in renal transplantation allowing to detect it at the "subclinical" stage.
Primary and secondary objectives:
The main objective of this study is to estimate the performance of MPE plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA. The secondary objective is to investigate by mass spectrometry the MPEs specific to the endothelium of the graft and to evaluate their diagnostic performance in relation to non-specific MEPs
Methodology :
We will conduct a cross-sectional evaluation of a diagnostic method from a collection of biological samples. The gold standard for the diagnosis of humoral rejection is the histological diagnosis on graft biopsy. The new test under study will be the flow cytometric assay of the MPE concentration carried out on plasma taken on the day of the graft biopsy.
Feasibility:
Among the active list of renal transplant patients attending the Montpellier University Hospital, we estimate that we can include the number of subjects required (N = 250) over 18 months. This work will be carried out in a laboratory with all the tools and techniques used, in particular flow cytometry and mass spectrometry, perfectly mastered and realized on dedicated technical platforms
Benefits / Outlook:
find a non-invasive early diagnostic biomarker to detect humoral rejection from the "subclinical" stage in order to set up an adapted treatment as quickly as possible.
Detailed description
Context and rationale:
Antibody-mediated rejection is the leading cause of long-term renal graft loss. It's due to the production by the recipient of antibodies directed against antigens (belonging or not to the HLA system) present on the surface of the donor specific endothelial cells (DSA), the binding of which can activate the renal endothelium and be responsible for inflammation leading to fibrosis and graft destruction.
The main obstacle in the management of the humoral rejection is the delay of the diagnosis and the treatment to slow the evolution towards fibrosis. At the beginning of the process there is no "apparent" dysfunction of the graft (elevation of serum creatinine and / or proteinuria) but only inflammation of the renal parenchyma: this is referred to as "subclinical" humoral rejection. Graft dysfunction occurs only when the inflammation is serious and responsible for irreversible lesions of fibrosis.
New sensitive detection techniques for anti-HLA antibodies allow to detect DSA well before the onset of humoral rejection but the only way to make the diagnosis of humoral rejection is to perform a graft biopsy, an invasive process with a hemorrhagic risk which can not be repeated too frequently.
Endothelial microparticles (MPE) are small membrane vesicles generated by endothelial cell activation and / or apoptosis processes. An increasing level in circulating blood appears today as a endothelial dysfunction in many pathologies. Their role in humoral rejection, a model of endothelial dysfunction, has never been explored.
We wish to test the hypothesis that endothelial microparticles are an early diagnostic biomarker of humoral rejection in renal transplantation allowing to detect it at the "subclinical" stage.
Primary and secondary objectives:
The main objective of this study is to estimate the performance of MPE plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA. The secondary objective is to investigate by mass spectrometry the MPEs specific to the endothelium of the graft and to evaluate their diagnostic performance in relation to non-specific MEPs
Methodology :
We will conduct a cross-sectional evaluation of a diagnostic method from a collection of biological samples. The gold standard for the diagnosis of humoral rejection is the histological diagnosis on graft biopsy. The new test under study will be the flow cytometric assay of the MPE concentration carried out on plasma taken on the day of the graft biopsy.
Feasibility:
Among the active list of renal transplant patients attending the Montpellier University Hospital, we estimate that we can include the number of subjects required (N = 250) over 18 months. This work will be carried out in a laboratory with all the tools and techniques used, in particular flow cytometry and mass spectrometry, perfectly mastered and realized on dedicated technical platforms
Benefits / Outlook:
At a time when the shortage of organs is growing and becomes a real public health problem, it becomes essential to better control the management of humoral rejection, the main cause of long-term renal graft loss. One of the key steps in this step is to find a non-invasive early diagnostic biomarker to detect humoral rejection from the "subclinical" stage in order to set up an adapted treatment as quickly as possible.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients without humoral rejection or DSA | Other | Biological: Biological sampleRenal transplant patients with systematic kidney biopsy at 3 months and 12 months Patients without humoral rejection or DSA (Donor Specific Antibodies) |
| Patient without humoral rejection with a DSA | Other | Biological: Biological samplePatient without humoral rejection with a DSA (Donor Specific Antibodies)Patients with a graft biopsy for a donor-specific anti-HLA antibody |
| Patients with humoral rejection | Other | Biological: Biological samplePatients with humoral rejection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age greater than or equal to 18 years at time of inclusion
- Renal transplant patients monitored at Montpellier University Hospital
- With a recent or planned realization of a graft biopsy
- Patients with DSA (s) detected by Single Antigen Bead Assay (SAB, LabScreen Single Antigen, One Lambda Kit) with an average fluorescence intensity> 500 IU Or Patients without DSA transplanted to a year with a systematic biopsy aspiration.
Key exclusion criteria (9 listed)
- Refusal to participate in or to undergo the examination
- Major protected by guardianship
- History of treated humoral rejection
- Incompatible graft ABO
- 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 |
|---|---|---|
| Biological sampleBiological sampling of two citrate tubes (18 ml) during a normal blood | Biological | Patient without humoral rejection with a DSA, Patients with humoral rejection, Patients without humoral rejection or DSA |
Primary outcome
Plasma concentration of endothelial microparticles
Time frame: 1 day
Endothelial microparticle (MPE) plasma concentration for the diagnosis of humoral rejection in renal transplant patients with DSA.
1 secondary outcome
Presence of specific MEPs
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
- Individual participant dataSharing planned: Undecided. NC
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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.
Moglie LE QUINTREC DONNETTE study director
University Hospital, Montpellier
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biological sample in people with Renal Transplantation, run by University Hospital, Montpellier 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 9 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: finished, as of the sponsor's last update on 14 Dec 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Plasma concentration of endothelial microparticles (time frame: 1 day). 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 14 Dec 2022.