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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Mai Aboelyazed El-Gebaly, Associate Lecturer
- Telefonní číslo: 020 +0201061412257
- E-mail: dr.mai.elgebaly@gmail.com
Studijní záloha kontaktů
- Jméno: Mai Aboelyazed Elgebaly, Associate Lecturer
- Telefonní číslo: 020 +201115064114
- E-mail: dr.mai.elgebaly@gmail.com
Studijní místa
-
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Elgharbeya
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Tanta, Elgharbeya, Egypt, GHR
- Tanta University
-
Kontakt:
- Mai Aboelyazed El-Gebaly, Associate Lecturer
- Telefonní číslo: 020 010-6141-2257
- E-mail: dr.mai.elgebaly@gmail.com
-
Kontakt:
- Mai Aboelyazed Elgebaly, Associate Lecturer
- Telefonní číslo: 020 011-1506-4114
- E-mail: dr.mai.elgebaly@gmail.com
-
Dílčí vyšetřovatel:
- Haidy Mahmoud Sami, Lecturer
-
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Prevence
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Komparátor placeba: Placebo Arm
Control Arm: Participants will receive standard oncological care without prophylactic linagliptin. |
Standard oncologic care without cardioprotective intervention followed concurrently for 24 weeks |
|
Experimentální: 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 |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Cardiac Troponin Assessment
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: Haidy Mahmoud Sami, Lecturer, Delta University
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Kardiovaskulární choroby
- Rány a zranění
- Patologické procesy
- Srdeční choroba
- Chemicky indukované poruchy
- Vedlejší účinky a nežádoucí účinky související s léky
- Radiační zranění
- Patologické stavy, příznaky a symptomy
- Kardiotoxicita
- Organické chemikálie
- Uhlovodíky
- Uhlovodíky, cyklické
- Uhlohydráty
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Glykosidy
- Antracykliny
- Nafthacenes
- Aminoglykosidy
- Daunorubicin
- Doxorubicin
Další identifikační čísla studie
- Delta University
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
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.
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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