Specific Genotypes/Phenotypes of Pneumocystis Jirovecii in Solid Organ Transplant Recipients: Potential Involvement of Mycophenolic Acid (IMPDH)
Emergence of Specific Genotypes/Phenotypes of Pneumocystis Jirovecii in Solid Organ Transplant Recipients: Potential Involvement of Mycophenolic Acid
調査の概要
詳細な説明
Mycophenolic acid (MPA) targets inosine 5'-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who are otherwise at risk for Pneumocystis pneumonia (PCP). We recently hypothesized that MPA exerts selective pressure on Pneumocystis given the in vitro antifungal activity of this drug on other fungi. In a single center study, we identified a missense mutation G1020A in the impdh gene, corresponding to an amino acid change Ala261Thr in IMPDH protein, among Pneumocystis isolates from MPA-treated SOT recipients. Considering that the IMPDH of MPA-resistant Candida albicans isolates harbors Thr at the analogous position, this mutation was considered to be a marker of Pneumocystis strain selection related to MPA exposure.
The aim of this study is to strengthen these preliminary results with data from a large multicenter study.
The study will be conducted in 26 centers in France. About one hundred patients with PCP will be enrolled. Pneumocystis isolates from SOT recipients exposed to MPA and from control patients (non-SOT recipients, not exposed to MPA) will be examined.The analysis of the impdh gene was combined with a multilocus sequence typing (MLST) method (mtLSUrRNA, cytochrome b and superoxide dismutase genes) characterized by a high discriminatory power.
The expected results may show the presence of the G1020A mutation (Ala261Thr) in SOT recipients exposed to MPA and in none of the control patients not exposed to MPA. This mutation will be significantly associated with MPA exposure. It could also be associated with a specific multilocus genotype in SOT patients and none of the control patients.
The study will confirm that the G1020A mutation (Ala261Thr) represents the signature of MPA exposure. The results of the analysis of the impdh gene combined with the MLST will highlight the selection under MPA pressure of specific strains of Pneumocystis, which circulate in the population of SOT recipients.
研究の種類
入学 (予想される)
連絡先と場所
研究連絡先
- 名前:Gilles nevez
- 電話番号:02 98 14 51 02
- メール:gilles.nevez@chu-brest.fr
研究連絡先のバックアップ
- 名前:solene Le Gall
- メール:solene.legal@univ-brest.fr
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- >= 18 years old with PCP diagnoses, organ transplant recipient or not, acceptation to participate
Exclusion Criteria:
- < 18 years old, no acceptation to participate
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Presence of Pneumocystis IMPDH gene mutant or not
時間枠:At patient enrollment
|
The main biological parameter which will be measured will be the positive or negative result for the detection of Pneumocystis IMPDH gene mutant
|
At patient enrollment
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (予想される)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- IMPDH ( 29BRC22.0106)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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