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Cardioprotection Effect of Linagliptin (Linagliptin)

2026年10月9日 更新者：Mai Abo Elyazeed Hassan Hamouda、Tanta University

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.

研究概览

地位

尚未招聘

条件

干预/治疗

详细说明

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.

研究类型

介入性

注册 (估计的)

140

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 埃及
    • Elgharbeya
      • Tanta、Elgharbeya、埃及、GHR
        • Tanta University
        • 接触：
        • 接触：
        • 副研究员：
          • Haidy Mahmoud Sami, Lecturer

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

女性

描述

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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：预防
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
安慰剂比较：Placebo Arm

Control Arm: Participants will receive standard oncological care without prophylactic linagliptin.
药品：Doxorubicin

Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks
实验性的：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.
药品：Doxorubicin

Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks

药品：Empaglifloz 5 mg orally once daily

Initiated 1 week prior to chemotherapy; continued for 24 weeks

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Cardiac Troponin Assessment
大体时间：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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Tanta University

调查人员

  • 研究主任：Haidy Mahmoud Sami, Lecturer、Delta University

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

  • 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.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年10月1日

初级完成 (估计的)

2028年10月31日

研究完成 (估计的)

2028年12月31日

研究注册日期

首次提交

2026年9月23日

首先提交符合 QC 标准的

2026年9月23日

首次发布 (实际的)

2026年10月1日

研究记录更新

最后更新发布 (实际的)

2026年10月15日

上次提交的符合 QC 标准的更新

2026年10月9日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • Delta University

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

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.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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