Breast cancer Doxorubicin Cardiotoxicity Mitochondria Breast cancer
Conditions
Interventions
The placebo drug is composed of Maize starch
,Metformin,
an anti-
diabetic drug,
has been proven to be a cardioprotective agent in clinical trial of diabetes mellitus. It has multiple modes of actions involving AMPK-
dependent and AMPK-
independent pathways. Evidence from in vitro studies and animal models indicated that metformin could protect against doxorubicin-
induced cardiotoxicity . The proposed mechanisms are through its antioxidant effects and inhibition of apoptotic pathway [33]. Additionally,
metformin could preserve cellular energy in doxorubicin model and exerts cardioprotective effects by activation of AMPK [32,
34]. This findings strengthen the role of metformin in the prevention of doxorubicin-
induced cardiotoxicity. To date,
there is no clinical study that investigate the cardioprotective effects of metformin in doxorubicin model.,Donepezil is the leading drug for treatment of Alzheimer’s disease. It blocks the degrada
recent study showed that Alzheimer’s disease patients treated with donepezil had a lower risk of cardiovascular mortality. This effect could be due to the stimulation of parasympathetic activity by
there is no study investigating role of donepezil in the prevention of doxorubicin-
induced cardiomyopathy.
Placebo,Metformin,Donepezil
Sponsors
National Science and Technology Development Agency
The Faculty of Medicine Endownment Fund
Eligibility
Sex/Gender
Female
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1) Female patient age > 18 years 2) Diagnosis with breast cancer and planned to receive doxorubicin 3) Given informed consent
Exclusion criteria
Exclusion criteria: 1 Metastatic breast cancer at diagnosis (except lymph node and bone metastasis) 2 Other malignancies 3 Prior history of chemotherapy or chest wall radiation 4 Prior cardiovascular disease with LVEF < 53% or severe valvular heart disease 5 CrCl < 30 ml/min as measured by Cockcroft-Gault Equation 6 Patients with baseline EKG show corrected QT interval > 500 msec 7 Patients currently receiving metformin or donepezil 8 Allergy or contraindication to metformin or donepezil 9 Life expectancy < 1 year 10 Pregnancy and lactating
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Troponin-I About 2 weeks after completion of doxorubicin therapy Troponin-I level | — |
Secondary
| Measure | Time frame |
|---|---|
| Cardiac function and biomarker 2 weeks post doxorubicin, month 3, month 6, month 9, month 12 Echocardiogram for LVEF and GLS, NT-proBNP level, Holter monitoring for HRV result,Markers of mitochondria dynamics, mitochondria function and apoptosis Post chemo C2, C4, C6 - Mitochondrial respiration (Seahorse), Mitochondrial ROS production, Annexin V ,Plasma antioxidant ,Genes associated with doxorubicin-induced cardiotoxicity at baseline PCR for gene analysis of single nucleotide polymorphism | — |
Countries
Thailand
Contacts
Public ContactNichanan Osataphan
Faculty of Medicine, Chiang Mai Uniiversity
Outcome results
None listed