Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06427226
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-23
First Post:
2024-05-18
Brief Title:
Evaluation of the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity
Sponsor:
Tanta University
Organization:
Tanta University
Study Overview
Official Title:
Clinical Study to Evaluate the Possible Safety and Efficacy of Dapagliflozin in the Prophylaxis of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a randomized controlled clinical trial that aims to evaluate the safety and efficacy of Dapagliflozin as a cardioprotective in doxorubicin-induced cardiotoxicity in breast cancer patients
Detailed Description:
Breast cancer is the most common type of cancer in women and the first cause of cancer death among them In Egypt it represents 33of female cancer cases and more than 22000 new cases are diagnosed each year This is expected to rise exponentially over the next years given the enlarging population and changes in the population pyramid
The Early Breast Cancer Trialists Collaborative Group EBCTCG reported that the inclusion of anthracyclines as doxorubicin in the management of breast cancer improved absolute survival by approximately 3 at 5 years and 4 at 10 years Therefore anthracyclines remain the cornerstone of treatment for breast cancer patients
Despite its effectiveness doxorubicin is associated with cumulative dose-dependent and potential cardiotoxicity
Although the main mechanism of doxorubicin-induced cardiotoxicity has not been fully known there are several mechanisms proposed for cardiac injury including oxidative stress free radical generation and apoptosis are most widely reported Other mechanisms are also involved such as impaired mitochondrial function perturbation in iron regulatory protein disruption of Ca2 homeostasis autophagy and the release of nitric oxide and inflammatory mediators
Dapagliflozin DAPA a sodium-glucose cotransporter 2 SGLT2 inhibitor is a class of glucose-lowering agents and is used to treat patients with type 2 diabetes Besides reducing glucose reabsorption DAPA has shown protective effects on cardiovascular diseases The cardioprotective effects of DAPA have been demonstrated in patients with diabetic cardiomyopathy heart failure HF with preserved ejection fraction EF and HF with reduced EF SGLT2 inhibitors exert their cardioprotective effect by increasing energy metabolism mitochondrial biogenesis autophagy and ketone bodies while decreasing endoplasmic reticulum ER stress ferroptosis oxidative stress and inflammation
In a recent animal study DAPA protected against doxorubicin-induced cardiotoxicity by reducing ER stress as evidenced by the decreased expression of the ER-related proteins including glucose-regulated protein 78 protein kinase R-like endoplasmic reticulum kinase and transcription factor 4
Doxorubicin administration have been shown to increase HF incidence HF admissions and the development of cardiomyopathy which is defined by a decline in left ventricle ejection fraction and these outcomes were attenuated by SGLT2 inhibitors
It is known that doxorubicin increases the circulating level of N-terminal pro-B-type natriuretic peptide NT-pro-BNP and cardiac Troponin T cTnT which DAPA significantly reduced in a recent animal study
The Early Breast Cancer Trialists Collaborative Group EBCTCG reported that the inclusion of anthracyclines as doxorubicin in the management of breast cancer improved absolute survival by approximately 3 at 5 years and 4 at 10 years Therefore anthracyclines remain the cornerstone of treatment for breast cancer patients
Despite its effectiveness doxorubicin is associated with cumulative dose-dependent and potential cardiotoxicity
Although the main mechanism of doxorubicin-induced cardiotoxicity has not been fully known there are several mechanisms proposed for cardiac injury including oxidative stress free radical generation and apoptosis are most widely reported Other mechanisms are also involved such as impaired mitochondrial function perturbation in iron regulatory protein disruption of Ca2 homeostasis autophagy and the release of nitric oxide and inflammatory mediators
Dapagliflozin DAPA a sodium-glucose cotransporter 2 SGLT2 inhibitor is a class of glucose-lowering agents and is used to treat patients with type 2 diabetes Besides reducing glucose reabsorption DAPA has shown protective effects on cardiovascular diseases The cardioprotective effects of DAPA have been demonstrated in patients with diabetic cardiomyopathy heart failure HF with preserved ejection fraction EF and HF with reduced EF SGLT2 inhibitors exert their cardioprotective effect by increasing energy metabolism mitochondrial biogenesis autophagy and ketone bodies while decreasing endoplasmic reticulum ER stress ferroptosis oxidative stress and inflammation
In a recent animal study DAPA protected against doxorubicin-induced cardiotoxicity by reducing ER stress as evidenced by the decreased expression of the ER-related proteins including glucose-regulated protein 78 protein kinase R-like endoplasmic reticulum kinase and transcription factor 4
Doxorubicin administration have been shown to increase HF incidence HF admissions and the development of cardiomyopathy which is defined by a decline in left ventricle ejection fraction and these outcomes were attenuated by SGLT2 inhibitors
It is known that doxorubicin increases the circulating level of N-terminal pro-B-type natriuretic peptide NT-pro-BNP and cardiac Troponin T cTnT which DAPA significantly reduced in a recent animal study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None