Clinical Study Evaluating Cardioprotective Effect of Melatonin Versus Vitamin D in Breast Cancer Patients Receiving Doxorubicin
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Tanta University
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Decreasing incidence and severity of cardiotoxicity
Study Overview
Brief Summary
This study aims to assess the cardioprotective effect of melatonin and vitamin D in breast cancer patients who receive doxorubicin.
Detailed Description
Doxorubicin is one of the most potent chemotherapeutic agents and is widely used for the treatment of various cancers and hematological malignancies . Although Doxorubicin has a potential beneficial effect in cancer treatment, its dose-dependent cardio toxicity is considered a major challenge.
Doxorubicin is known to generate free radicals either by redox cycling between a semiquinone form and a quinone form or by forming a Doxorubicin-Fe3+ complex . In both pathways, molecular oxygen is reduced to superoxide ion , which is converted to other forms of reactive oxygen species such as hydrogen peroxide and hydroxyl radical . These free radicals could then cause membrane and macromolecule damage, both of which lead to injury to the heart, an organ that has a relatively low level of antioxidant enzymes such as superoxide dismutase and catalase .
Furthermore, it was revealed that Doxorubicin may enhance the death of cardiomyocytes by affecting the tumor necrosis factor signaling pathway via increasing the expression and levels of inflammatory genes interleukin and interleukin -6 .
To alleviate DOX-induced toxicity, researchers have tested a number of strategies, including the administration of antioxidants and/or antiapoptotic agents, in both in vitro and in vivo models of Doxorubicin induced cytotoxicity, but most of these trials have failed to translate into clinical benefits . As a result, there are no effective approaches for alleviating Doxorubicin induced cytotoxicity despite intensive research over recent decades .
Melatonin is a natural hormone that is primarily secreted by the pineal gland and functions as a major regulator of circadian rhythms in humans . Melatonin also plays a variety of biological roles as a modulator of mood, sexual behavior and sleep; low levels or a deficiency of melatonin are also associated with Parkinson's disease, Alzheimer's disease, epilepsy, ischemic injury, diabetes, and even cancer .
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age from 18 to 65 years old.
- •Gender: female.
- •Positive breast cancer women who are scheduled to receive Doxorubicin.
- •Have a good performance status according to the eastern cooperative oncology group with a score of 0-
- •Normal baseline Echocardiography with left ventricular ejection fraction ≥ 50%.
- •Normal renal and liver function tests.
Exclusion Criteria
- •Pregnant or breastfeeding women.
- •Women with HER-2 positive of breast cancer.
- •Formerly treated with Doxorubicin.
- •Patients with a known hypersensitivity to any of the used drugs.
- •On other concomitant vitamins or food supplements.
- •Valvular heart disease, coronary artery disease, history of congestive heart failure or cardiomyopathy.
- •Impaired Left ventricular systolic function in which the Left Ventricular Ejection Fraction < 50%.
Arms & Interventions
Group 1 (Doxorubicin group)
30 patients will receive a traditional chemotherapeutic agent (Doxorubicin group) for 12 weeks.
Intervention: Group 1 (Doxorubicin group) (Drug)
Group 2 (Vitamin D group)
patients with Vitamin D supplementation (1000 iu/day) plus Doxorubicin for 12 weeks
Intervention: Group 2: Vitamin D group (Drug)
Group 3 (melatonin group)
30 patients with 10 mg of melatonin orally, once daily plus Doxorubicin for 12 weeks.
Intervention: Group 3: melatonin group (Drug)
Outcomes
Primary Outcomes
Decreasing incidence and severity of cardiotoxicity
Time Frame: 12 weeks
Assessment of decreasing incidence and severity of cardiotoxicity by echocardiogram and ejection fraction is associated with doxorubicin treatment.
Secondary Outcomes
- change in the serum level of the (biological markers).(12 weeks)
Investigators
Majed Essa Alharbi
Resident
Tanta University