Liver Immune Tolerance Marker Utilization Study (LITMUS)
調査の概要
詳細な説明
Previous pre-clinical work in the Levy Lab identified a novel biomarker gene set for the identification of tolerance in murine models of rapamycin-induced cardiac tolerance and spontaneous hepatic tolerance. Validation of this gene expression tolerance biomarker in operationally tolerant patients is now required for its implementation in the clinical setting. This proposal intends to validate and test our pre-clinically established tolerance gene expression biomarker in the clinical setting in order to translate our findings into improving the length and quality of life of transplant patients in the clinic.
The investigators hypothesize that a distinct gene expression profile expressed in the peripheral blood will identify operationally tolerant liver transplant recipients, allowing for the successful withdrawal of immunosuppression in these patients. Our study aims are: (I) To validate the pre-clinical gene expression profile for the identification of operationally tolerant liver recipients in plasma peripheral blood mononuclear cells (PBMCs) (2) To determine that the gene expression profile in the PBMCs is the same as the intra-graft gene expression profile (3) To demonstrate that liver transplant recipients with the tolerant gene expression profile can be safely weaned off of immunosuppression.
This proof of principle study will be conducted in two phases at the Toronto General Hospital (TGH) Phase 1 will address study aims 1 and 2, and phase 2 will address study aim 3. Potential participants will be screened and selected following predefined eligibility criteria. Eligible participants will undergo an informed consent process. The primary goal of this study is to validate the pre-clinical tolerant gene expression profile that will allow for the identification of tolerant liver recipients and for the monitored weaning off immunosuppression in these tolerant patients.
研究の種類
入学 (実際)
段階
- 適用できない
連絡先と場所
研究場所
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Ontario
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Toronto、Ontario、カナダ、M5G 2C4
- Toronto General Hospital
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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
説明
Inclusion Criteria:
To be eligible to participate in this study, patients must:
- Be between 18 and 65 years of age.
- Be recipients of a hepatic allograft.
- Be less than 3 months post-transplant and be experiencing rejection, or be a minimum of 3 months post-transplant with or without presently experiencing rejection.
- Be healthy live liver donors
Exclusion Criteria:
Patients with the following conditions may not participate in the study:
- Patients under the age of 18 and over the age of 65.
- Patients who are positive for Human Immunodeficiency Virus (HIV),
- Patients who have detectable levels of HCV RNA, and HBV DNA, at the time of enrollment.
- Patients who have a combined transplant and/or have been re-transplanted.
- Patients taking immunosuppression for other diseases besides their liver transplant.
- Patients unable to give written informed consent in accordance with research ethics board guidelines.
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
- 主な目的：診断
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Controlled weaning of immunosuppression
Participants who are found to have the tolerance gene expression profile during phase 1 of the study will undergo closely monitored immunosuppression weaning during phase 2.
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At week 0 patients have liver biopsy and liver functional tests (LFTs).
Week 1-4 medication reduction to 1.5mg Tacrolimus (Tac) daily or 150mg Cyclosporine A (CsA).
At week 4 LFTs.
Week 5-8 medication reduction to 1mg Tac / 100mg CsA.
Week 8 LFTs.
Week 9-12 reduction to 0.5mg Tac/ 50mg CsA.
Week 12 LFTs.
Week 13-16 reduction to 0mg.
Week 16 liver biopsy & LFTs.
Weekly LFTs performed Week 17-20.
Monthly LFTs for the next 3 months.
LFTs every 3 months for monitoring.
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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 |
|---|---|---|
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Validation of Tolerance Gene Expression Profile
時間枠：Enrollment to one year post cessation of immunosuppression
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The primary endpoint of this study is the identification and validation of a unique tolerance gene expression profile, consisting of a 6 gene profile, in 3-6 operationally tolerant patients compared to 25 rejecting and 25 healthy controls.
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Enrollment to one year post cessation of immunosuppression
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Tolerance gene expression profile in graft versus peripheral blood mononuclear cells (PBMCs)
時間枠：Enrollment to one year post cessation of immunosuppression
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This endpoint will be defined as the ratio of patients (n=55) that will express the tolerance gene expression profile in the liver graft versus in the peripheral blood mononuclear cells.
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Enrollment to one year post cessation of immunosuppression
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Test of tolerance gene expression profile
時間枠：Enrollment to one year post cessation of immunosuppression
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This endpoint will assess whether the tolerance gene expression profile can be successfully used to select immunosuppressed patients for the successful weaning off immunosuppression.
This endpoint will be evaluated using the number of successful immunosuppression-weaned patients from a 7-10 patient cohort.
Successful immunosuppression-weaned patients are defined as patients who achieve an immunosuppression free state without any histological or clinical evidence of rejection for a minimum of 1 year.
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Enrollment to one year post cessation of immunosuppression
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協力者と研究者
スポンサー
捜査官
- 主任研究者：Gary Levy, M.D.、University Health Network, University of Toronto
- スタディチェア：Leslie Lilly, M.D.、University Health Network, Toronto
- スタディチェア：Nazia Selzner, M.D. PhD.、University Health Network, Toronto
- スタディディレクター：Meaghan MacArthur, M.Ed、University Health Network, Toronto
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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 (見積もり)
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
キーワード
その他の研究ID番号
- Tol002
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