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Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation (ECLAT)
Chronic renal failure is a major public health problem in industrialized countries, due to its frequency - about 3 million patients in France - and its socio-economic impact. At the end stage of renal failure, renal transplantation is the best treatment, allowing an improvement in patient survival compared to treatment by extra-renal purification. Despite improved immunosuppressive strategies, allograft rejection is common in transplantation - between 15% and 25% in the first year - and is associated with lower renal graft survival.
Different risk factors for rejection have been well identified, such as the young age of the recipient or a high number of human leukocyte antigen (HLA) incompatibilities between the donor and the recipient. However, these risk factors do not accurately identify the risk of acute rejection in order to optimize and individualize immunosuppressive strategies.
Also, the search for biomarkers to predict allograft tolerance prior to transplant is a major goal in renal transplantation.
The onset of acute rejection is caused by the ability of the recipient's T cells to recognize alloantigens. The CD45 molecule is a highly expressed tyrosine phosphatase on the surface of the lymphocytes that plays an important role in the activation of the T cell.
Investigators showed that the level of expression of CD45RC on T lymphocytes was associated with the risk of acute rejection. Thus, from a retrospective cohort of 89 renal transplant patients followed, recipients with a high percentage of circulating CD8 lymphocytes expressing high CD45RC (CD45RChigh) before transplant had a 5 to 8-fold higher risk of developing acute rejection of allograft during follow-up (11-year average follow-up) compared to recipients with a low percentage of CD8+CD45RChigh.
The purpose of this study is to confirm the first retrospective results on a larger prospective and contemporary regional cohort.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| End-stage Renal Disease | Other: Blood samples | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Screening |
| Official Title: | Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation |
| Estimated Study Start Date : | June 2020 |
| Estimated Primary Completion Date : | July 2023 |
| Estimated Study Completion Date : | July 2023 |
| Arm | Intervention/treatment |
|---|---|
| Patient in need of a kidney transplant |
Other: Blood samples
Blood samples the day of the surgery and 4 times during the next year. Blood samples and histological slides taken at each biopsy and if there is suspicion of rejection of the graft
|
- Number of patient with acute rejection diagnosis confirmed by anatomopathological analysis of a graft biopsy [ Time Frame: 12 months ]
- Rate of CD45RC for patient with acute rejection suspicion [ Time Frame: 12 months ]acute rejection confirmed or not
- Rate of CD45RC on circulating T lymphocytes [ Time Frame: from date of randomization until the date of acute rejection, up to 12 months ]Evolution of the expression of CD45RC in the first year after introduction of immunosuppressive therapy
- Rate of CD45RC on circulating T lymphocytes the day of acute rejection [ Time Frame: 12 months ]day of acute rejection
- Rate of CD4, CD8, CD45RA, CD25, CD127, CD19 markers on T cells the day of acute rejection [ Time Frame: 12 months ]day of acute rejection
- anti-HLA antibodies' dosage at the time of acute rejection [ Time Frame: 12 months ]
- cytokines' dosage [ Time Frame: Day 1 ]describe cytokine profile
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients over 18 and under 70 years old
- Patients in care for a first priority renal transplant.
- Patients with low immunological risk
- Patients with prior written informed consent
Exclusion Criteria:
- Poor understanding of the French language
- Pregnant, breastfeeding or partying women
- Persons deprived of liberty by an administrative or judicial decision
- Persons undergoing psychiatric care under duress
- Adults who are subject to a legal or non-state protection measure to express their consent
| Contact: Anne-Sophie GARNIER, MD | 0241356075 ext +33 | AnneSophie.Garnier@chu-angers.fr | |
| Contact: Béatrice GABLE | begable@chu-angers.fr |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 11, 2019 | ||||||||
| First Posted Date ICMJE | June 21, 2019 | ||||||||
| Last Update Posted Date | January 29, 2020 | ||||||||
| Estimated Study Start Date ICMJE | June 2020 | ||||||||
| Estimated Primary Completion Date | July 2023 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
Number of patient with acute rejection diagnosis confirmed by anatomopathological analysis of a graft biopsy [ Time Frame: 12 months ] | ||||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
|
||||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation | ||||||||
| Official Title ICMJE | Evaluation of the Level of Expression of CD45RC on T Lymphocytes as a Predictive Biomarker of Acute Rejection After Renal Transplantation | ||||||||
| Brief Summary |
Chronic renal failure is a major public health problem in industrialized countries, due to its frequency - about 3 million patients in France - and its socio-economic impact. At the end stage of renal failure, renal transplantation is the best treatment, allowing an improvement in patient survival compared to treatment by extra-renal purification. Despite improved immunosuppressive strategies, allograft rejection is common in transplantation - between 15% and 25% in the first year - and is associated with lower renal graft survival. Different risk factors for rejection have been well identified, such as the young age of the recipient or a high number of human leukocyte antigen (HLA) incompatibilities between the donor and the recipient. However, these risk factors do not accurately identify the risk of acute rejection in order to optimize and individualize immunosuppressive strategies. Also, the search for biomarkers to predict allograft tolerance prior to transplant is a major goal in renal transplantation. The onset of acute rejection is caused by the ability of the recipient's T cells to recognize alloantigens. The CD45 molecule is a highly expressed tyrosine phosphatase on the surface of the lymphocytes that plays an important role in the activation of the T cell. Investigators showed that the level of expression of CD45RC on T lymphocytes was associated with the risk of acute rejection. Thus, from a retrospective cohort of 89 renal transplant patients followed, recipients with a high percentage of circulating CD8 lymphocytes expressing high CD45RC (CD45RChigh) before transplant had a 5 to 8-fold higher risk of developing acute rejection of allograft during follow-up (11-year average follow-up) compared to recipients with a low percentage of CD8+CD45RChigh. The purpose of this study is to confirm the first retrospective results on a larger prospective and contemporary regional cohort. |
||||||||
| Detailed Description | Not Provided | ||||||||
| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Not Applicable | ||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Screening |
||||||||
| Condition ICMJE | End-stage Renal Disease | ||||||||
| Intervention ICMJE | Other: Blood samples
Blood samples the day of the surgery and 4 times during the next year. Blood samples and histological slides taken at each biopsy and if there is suspicion of rejection of the graft
|
||||||||
| Study Arms ICMJE | Patient in need of a kidney transplant
Intervention: Other: Blood samples
|
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| Publications * | Not Provided | ||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Not yet recruiting | ||||||||
| Estimated Enrollment ICMJE |
150 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | July 2023 | ||||||||
| Estimated Primary Completion Date | July 2023 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||||
| Sex/Gender ICMJE |
|
||||||||
| Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
|
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| Listed Location Countries ICMJE | Not Provided | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT03994497 | ||||||||
| Other Study ID Numbers ICMJE | 49RC18_0018 | ||||||||
| Has Data Monitoring Committee | Not Provided | ||||||||
| U.S. FDA-regulated Product |
|
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| IPD Sharing Statement ICMJE | Not Provided | ||||||||
| Responsible Party | University Hospital, Angers | ||||||||
| Study Sponsor ICMJE | University Hospital, Angers | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE | Not Provided | ||||||||
| PRS Account | University Hospital, Angers | ||||||||
| Verification Date | June 2019 | ||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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