Cardioprotective Effect of Melatonin Versus Vitamin D in Breast Cancer Patients Receiving Doxorubicin

Clinical Study Evaluating Cardioprotective Effect of Melatonin Versus Vitamin D in Breast Cancer Patients Receiving Doxorubicin

This study aims to assess the cardioprotective effect of melatonin and vitamin D in breast cancer patients who receive doxorubicin.

Study Overview

• Status: Not yet recruiting
• Conditions: Melatonin; Doxorubicin; Vitamin D Concentration; Breast Cancer Patients Diagnosed
• Intervention / Treatment: Drug: Group 1 (Doxorubicin group); Drug: Group 2: Vitamin D group; Drug: Group 3: melatonin group

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 .

Melatonin has emerged as a promising adjuvant that protects against doxorubicin-induced cytotoxicity, as highlighted by various studies and clinical trials that have demonstrated cardioprotective effects against several chemotherapeutic agents . Moreover, melatonin exhibits low toxicity and easily enters cells owing to its good solubility in both aqueous and organic phases and its highly lipophilic properties . Vitamin D plays an important role in the regulation of body function including the cardiovascular system .

Vitamin D deficiency results in the decrease of active calcitriol leading to inhibition of proliferation of cardiomyocytes and vascular smooth muscles .

This study aims to assess the cardioprotective effect of melatonin and vitamin D in breast cancer patients who receive doxorubicin.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Majed Alharbi, Resident; Phone Number: +966 55 189 8178; Email: Ph.majed33@gmail.com

Study Locations

• Egypt
  • Tanta, Egypt
    • Tanta University
    • Contact: Majed Essa Alharbi, Resident; Phone Number: +966 55 189 8178; Email: Ph.majed33@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 0-2.
• 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%.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1 (Doxorubicin group); 30 patients will receive a traditional chemotherapeutic agent (Doxorubicin group) for 12 weeks.	Drug: Group 1 (Doxorubicin group); 30 patients will receive a traditional chemotherapeutic agent (Doxorubicin group) for 12 weeks.
Experimental: Group 2 (Vitamin D group); patients with Vitamin D supplementation (1000 iu/day) plus Doxorubicin for 12 weeks	Drug: Group 2: Vitamin D group; patients with Vitamin D supplementation (1000 iu/day) plus traditional therapy for 12 weeks
Experimental: Group 3 (melatonin group); 30 patients with 10 mg of melatonin orally, once daily plus Doxorubicin for 12 weeks.	Drug: Group 3: melatonin group; patients with 10 mg of melatonin orally, once daily plus traditional therapy for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decreasing incidence and severity of cardiotoxicity	Assessment of decreasing incidence and severity of cardiotoxicity by echocardiogram and ejection fraction is associated with doxorubicin treatment.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
change in the serum level of the (biological markers).	12 weeks

Collaborators and Investigators

• Sponsor: Tanta University

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: January 9, 2026
• First Submitted That Met QC Criteria: January 9, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Vitamin D; Melatonin; Doxorubicin; Breast Cancer Patients; Cardioprotective Effect
• Other Study ID Numbers: 36265MD408/5/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data will be available when needed
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No