INTERCOMEX Donor-Derived Cell Free DNA Study
キーワード
概要
説明
There is a need for better screening of kidney transplant patients for rejection. Patients with kidney transplants are routinely tested (creatinine, urine protein, histology and donor specific antibody (DSA) as standard of care to detect rejection, but these tests are not adequate. Rejection is often missed by these tests (false negatives) and other processes such as acute kidney injury can produce false-positive results. Moreover, histology has a high interobserver disagreement diagnosing rejection, and cannot accurately assess acute injury. A definitive molecular assessment of rejection and injury in kidney biopsies has emerged - the Molecular Microscope® Diagnostic System (MMDx) - developed by the Alberta Transplant Applied Genomics Centre, University of Alberta. Now a new screening test is being introduced: the monitoring of donor-derived cell-free DNA (DD-cfDNA) released in the blood by the kidney during rejection. The Natera Inc DD-cfDNA Prospera® test is based on the massively multiplex PCR that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test done on kidney transplant recipients detected "active rejection" and differentiated it from borderline rejection and no rejection. It is likely, however, that DD-cfDNA test may miss some T cell-mediated rejection (TCMR) cases and the distinction between early and fully developed antibody-mediated rejection (ABMR) was not tested. No study has actually examined the DD-cfDNA results in kidney transplants with acute or chronic kidney disease (AKI and CKD). DD-cfDNA measurements have only been correlated with histology, a flawed standard. DD-cf-DNA test must now be calibrated against MMDx that is based on global gene expression, the new standard for biopsy interpretation. The present study will calibrate centrally measured (Natera Inc) DD-cfDNA levels obtained at the time of an indication biopsy against the MMDx measurements of TCMR, and ABMR (early-stage, fully-developed, and late-stage), AK, and atrophy-fibrosis. We will compare blood DD-cfDNA measurements in 600 samples at the time of 300 indication biopsies to the MMDx results, as well as central assessment of HLA antibody (One Lambda) in 300 blood samples, interpreted as DSA by the center based on the tissue typing results. This study is an extension of the INTERCOMEX ClinicalTrials.gov Identifier: NCT01299168
日付
最終確認済み: | 05/31/2020 |
最初に提出された: | 01/13/2020 |
提出された推定登録数: | 01/22/2020 |
最初の投稿: | 01/26/2020 |
最終更新が送信されました: | 06/22/2020 |
最終更新日: | 06/24/2020 |
実際の研究開始日: | 11/30/2019 |
一次完了予定日: | 05/31/2021 |
研究完了予定日: | 11/30/2021 |
状態または病気
介入/治療
Diagnostic Test: Kidney transplant biopsies for cause
Diagnostic Test: Kidney transplant biopsies for cause
Diagnostic Test: Kidney transplant biopsies for cause
段階
アームグループ
腕 | 介入/治療 |
---|---|
Kidney transplant biopsies for cause The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care. | Diagnostic Test: Kidney transplant biopsies for cause Portion of kidney transplant indication biopsy |
適格基準
研究に適格な性別 | All |
サンプリング方法 | Probability Sample |
健康なボランティアを受け入れる | はい |
基準 | Inclusion Criteria: - All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study. Exclusion Criteria: - Patients will be excluded from the study if they decline participation or are unable to give informed consent. |
結果
主な結果の測定
1. Calibration of Prospera test for T cell-mediated rejection [18 months]
2. Calibration of Prospera test for antibody-mediated rejection [18 months]
3. Calibration of Prospera test for kidney injury [18 months]
4. Report calibrated Prospera test results for rejection [6 months]
5. Report calibrated Prospera test results for kidney injury [6 month]
二次的な結果の測定
1. Determine if Prospera blood test can replace kidney biopsy test [6 months]
2. Assessment of donor-specific antibody status [6 months]