Cardioprotection Effect of Linagliptin (Linagliptin)
Cardio-protective Effect of Linagliptin in Women With Breast Cancer Receiving Doxorubicin-Based Chemotherapy
1. Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
調査の概要
詳細な説明
1. Background and Rationale Breast cancer is one of the most common malignancies affecting women worldwide and represents a major health burden in Egypt. Anthracyclines, particularly doxorubicin, remain an important component of several breast cancer chemotherapy regimens. However, their clinical utility is limited by the potential development of anthracycline-induced cardiotoxicity.
Doxorubicin-induced cardiac injury is multifactorial and involves oxidative stress, mitochondrial dysfunction, disturbances in myocardial energy metabolism, apoptosis, inflammation, and progressive myocardial structural damage. Cardiac injury may initially occur without symptoms or an obvious reduction in left ventricular ejection fraction (LVEF). Consequently, identification of early myocardial injury is important because intervention before clinically apparent heart failure may potentially reduce progression to overt cardiac dysfunction.
The European Society of Cardiology recommends cardiovascular assessment and surveillance in patients receiving potentially cardiotoxic cancer therapies. Cardiac troponin (cTn) and natriuretic peptides may be used as biomarkers of cancer therapy-related cardiovascular toxicity, while echocardiography, including LVEF and global longitudinal strain (GLS) where available, provides complementary information about cardiac function.
Cardiac troponin is a highly specific biomarker of myocardial injury. According to the Fourth Universal Definition of Myocardial Infarction, myocardial injury is defined by a cardiac troponin concentration above the assay-specific 99th-percentile upper reference limit, while an acute injury is characterized by a rise and/or fall in troponin values.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are primarily used as glucose-lowering agents in patients with type 2 diabetes mellitus. Linagliptin is a selective DPP-4 inhibitor administered at a standard dose of 5 mg once daily. Large cardiovascular-outcome data have demonstrated cardiovascular safety of linagliptin in patients with type 2 diabetes at high cardiovascular and renal risk, including no significant increase in hospitalization for heart failure compared with placebo.
However, whether linagliptin can prevent anthracycline-associated myocardial injury in women with breast cancer without diabetes remains insufficiently established. This creates a clinically relevant research gap.
Therefore, the proposed study will investigate whether prophylactic linagliptin, administered during doxorubicin-containing chemotherapy, can attenuate biochemical evidence of myocardial injury assessed by cardiac troponin and reduce the development of cardiac dysfunction.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Mai Aboelyazed El-Gebaly, Associate Lecturer
- 電話番号：020 +0201061412257
- メール：dr.mai.elgebaly@gmail.com
研究連絡先のバックアップ
- 名前：Mai Aboelyazed Elgebaly, Associate Lecturer
- 電話番号：020 +201115064114
- メール：dr.mai.elgebaly@gmail.com
研究場所
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Elgharbeya
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Tanta、Elgharbeya、エジプト、GHR
- Tanta University
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コンタクト：
- Mai Aboelyazed El-Gebaly, Associate Lecturer
- 電話番号：020 010-6141-2257
- メール：dr.mai.elgebaly@gmail.com
-
コンタクト：
- Mai Aboelyazed Elgebaly, Associate Lecturer
- 電話番号：020 011-1506-4114
- メール：dr.mai.elgebaly@gmail.com
-
副調査官：
- Haidy Mahmoud Sami, Lecturer
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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:
- Female patients aged ≥18 years.
- Egyptian nationality.
- Histologically confirmed breast cancer.
- Planned treatment with a doxorubicin-containing chemotherapy regimen.
- Expected cumulative doxorubicin dose of approximately ≥240 mg/m², or another prespecified protocol threshold.
- Baseline LVEF ≥53%.
- Adequate baseline echocardiographic assessment.
- Baseline cardiac troponin below the laboratory's predefined exclusion threshold.
- Ability to take oral medication.
- Ability to provide written informed consent.
- Willingness to comply with study visits, blood sampling and cardiac assessments.
Exclusion Criteria:
- Previous exposure to anthracyclines.
- Known heart failure.
- Baseline LVEF <53%.
- Previous myocardial infarction or significant coronary artery disease.
- Significant valvular heart disease.
- Clinically significant arrhythmia.
- Uncontrolled hypertension.
- Significant renal impairment according to a predefined eGFR threshold.
- Significant hepatic impairment.
- Active infection or another condition likely to affect troponin interpretation.
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：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- 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 |
|---|---|
|
プラセボコンパレーター：Placebo Arm
Control Arm: Participants will receive standard oncological care without prophylactic linagliptin. |
Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks |
|
実験的：Linagliptin Arm
Participants will receive: Linagliptin 5 mg orally once daily. The proposed treatment will begin before or at initiation of the first doxorubicin-containing chemotherapy cycle and continue throughout the predefined chemotherapy period. |
Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks Initiated 1 week prior to chemotherapy; continued for 24 weeks |
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 |
|---|---|---|
|
Cardiac Troponin Assessment
時間枠：3 months
|
The principal biochemical endpoint will be defined as: Cardiac troponin concentration >99th percentile upper reference limit of the laboratory assay. Acute myocardial injury will be characterized by a dynamic rise and/or fall in troponin when clinically appropriate. |
3 months
|
協力者と研究者
スポンサー
捜査官
- スタディディレクター：Haidy Mahmoud Sami, Lecturer、Delta University
出版物と役立つリンク
一般刊行物
- Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138(20):e618-e651. doi:10.1161/CIR.0000000000000617. Osataphan N, Phrommintikul A, Leemasawat K, Somwangprasert A, Apaijai N, Suksai S, et al. Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial. Sci Rep. 2023;13:12759. doi:10.1038/s41598-023-40061-4. McGuire DK, Alexander JH, Johansen OE, Perkovic V, Rosenstock J, Cooper ME, et al. Linagliptin effects on heart failure and related outcomes in individuals with type 2 diabetes mellitus at high cardiovascular and renal risk in CARMELINA. Circulation. 2019;139(3):351-361. doi:10.1161/CIRCULATIONAHA.118.038352. Rosenstock J, Perkovic V, Johansen OE, Cooper ME, Kahn SE, Marx N, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA. 2019;321(1):69-79. doi:10.1001/jama.2018.18249. Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, et al. Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol. 2010;28(25):3910-3916. doi:10.1200/JCO.2009.27.3615. Osataphan N, Phrommintikul A, Chattipakorn SC, Chattipakorn N. Effects of doxorubicin-induced cardiotoxicity on cardiac mitochondrial dynamics and mitochondrial function: insights for future interventions. J Cell Mol Med. 2020;24(12):6534-6557. doi:10.1111/jcmm.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
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
- Delta University
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Individual participant data (IPD) will not be made available to other researchers. The study data will be maintained securely by the research team and will be accessible only to authorized study investigators. Participant confidentiality and privacy will be strictly protected, and data will not be shared in a form that could permit identification of individual participants.
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米国FDA規制医薬品の研究
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