Melatonin Supplementation and Exercise Program in Breast Cancer Women

NCT ID: NCT06696378

Last Updated: 2024-11-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-15
• Study Completion Date: 2026-05-01

Brief Summary

Introduction: Breast cancer (BC) remains the leading cause of cancer in women with nearly 1.4 million new cases worldwide annually and 27.000 in Spain. Increasingly effective oncology therapies, however, have numerous adverse effects such as muscle degeneration, fatigue, decreased physical function and aerobic capacity, and deteriorating quality of life. In this sense, physical activity (PA) seems to be an interesting non-pharmacological strategy to alleviate these serious complications and with potential benefits for women with BC. Melatonin (N-acetyl-5 methoxytryptamine) is an indolic compound present with pleiotropic bioactions that regulates the circadian rhythm, antioxidant, anti-inflammatory, immunostimulant, cardioprotective, antidiabetic, antiobesity, neuroprotective, and antiaging actions. Furthermore, in recent years, many studies have described the key role of melatonin in preventing and developing cancer. The general anticarcinogenic mechanisms include epigenetic control, cell proliferation modulation, cell cycle regulation, apoptosis induction, and telomerase inhibition. Melatonin also exerts antiestrogenic activity, which is particularly significant in hormone-dependent tumors, regulating the expression and transactivation of the estrogen receptor, and modulating the enzymes involved in the local synthesis of estrogens. Despite all the mentioned properties, the use of melatonin in daily clinical practice is very limited, and additional studies are needed to better establish the role of this hormone in oncological clinical applications against different types of cancer.

Objective: To analyze the effect of supplementation with 4 g/day of melatonin for 10 weeks on muscle damage (CK and LDH), hormonal responses (estradiol, testosterone, cortisol and testosterone/cortisol ratio), antioxidant capacity (BAP and d-ROMs), Exerkins (Irisin and Sestrin 2), physical performance (handgrip strength, RPE and SPPB), anthropometry (body mass, BMI and fat mass) and WHOQOL-BREF (physical and psychological health, social relationships and environment) in women over 60 years of age who have suffered breast cancer and who follow a physical training program.

Methods: A total of 20 female volunteers between 60 and 73 years old (age: 65.5±4.52 years, BMI: 25.83±2.67 and body fat percentage: 33.73±5.54) who followed a physical activity adapted to their age and abilities are the members. of this study. The volunteers were divided into two groups: placebo (CG; n = 10) and supplemented with 5 g/day of melatonin (GI; n = 10). Differtent test were performed muscle damage (CK, and LDH), hormonal responses (estradiol, testosterone, cortisol, and testosterone/cortisol ratio), antioxidant capacity (BAP and d-ROMs), Exerkins (Irisin and Sestrin 2), physical performance (Hand-grip strength, RPE and SPPB), anthropometrics (Body mass, BMI and fat mass), and WHOQOL-BREF (physical and psychological health, social relationships and environment) were analyzed at the beginning (T1) and at the end of the 10 weeks of intervention (T2).

Conditions

Female Breast Cancer; Older Adults; Exercise Trainning Progrmam

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Melatonin supplementation group

2 capsules distributed in a single daily oral intake at 9 p.m. or 30 minutes before bedtime, whichever came first, for 10 weeks.

Group Type: EXPERIMENTAL

Melatonin 6 mg

Intervention Type: DIETARY_SUPPLEMENT

wo capsules per day; Each capsule includes 3mg Melatonin Nutrifoods® Laboratories, Barcelona, Spain) by the Magistral Formulation Laboratory of a Pharmacy (Soria, Spain), following the rules of the Royal Spanish Pharmacopoeia (Ministry of Health, Government of Spain). Melatonin has a technical data sheet that guarantees its composition and purity (Reference No.: DIE-134).

Placebo supplementation group

2 capsules distributed in a single daily oral intake at 9 p.m. or 30 minutes before bedtime, whichever came first, for 10 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Two capsules per day; Each capsule includes 100-mg maltodextrin capsules were used as a placebo to match the color and texture of the Melatonin tablets to ensure blinding.

Interventions

Melatonin 6 mg

wo capsules per day; Each capsule includes 3mg Melatonin Nutrifoods® Laboratories, Barcelona, Spain) by the Magistral Formulation Laboratory of a Pharmacy (Soria, Spain), following the rules of the Royal Spanish Pharmacopoeia (Ministry of Health, Government of Spain). Melatonin has a technical data sheet that guarantees its composition and purity (Reference No.: DIE-134).

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Two capsules per day; Each capsule includes 100-mg maltodextrin capsules were used as a placebo to match the color and texture of the Melatonin tablets to ensure blinding.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Study participants were women with a history of ductal carcinoma in situ, lobular carcinoma in situ, or stage 1 to 3 breast cancer (5 years or more since diagnosis), not currently receiving chemotherapy or hormone therapy, postmenopausal, and Eastern Cooperative Oncology Group (ECOG) score ≤ 1

Exclusion Criteria

• women who had exercised regularly for at least 20 minutes once and at least twice a week in the 3 months before the study
• Stage IV breast cancer or systemic recurrences
• Known autoimmune diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis.
• Severe kidney disease
• Use of adjuvant hormonal therapy, oral estrogen or progesterone replacement therapy, luteinizing hormone-releasing hormone agonists currently or within the past 60 days
• 6-month ≥ post-chemotherapy
• Concomitant use of sleeping pills every night at bedtime
• Concomitant use of black cohosh, flaxseed, or soy in pill or supplement form
• Functional limitation using the Barthel scale (less than 100 = maximum score) and the Lawton-Brody scale (less than 8 = maximum value).
• Uncontrolled hypertension (>180/100 mm Hg).
• Uncontrolled atrial or ventricular arrhythmias, dissecting aortic aneurysm, severe aortic stenosis, acute endocarditis/pericarditis
• Acute thromboembolic disease.
• Moderate/severe chronic obstructive pulmonary disease (COPD) with Bodex index C or D Recent bone fracture (last month).
• Any other circumstance that your doctor considers prevents physical activity.
• Neoadjuvant chemotherapy or radiotherapy
• Concomitant use of beta-blockers
• 6-month ≥ post-radiotherapy
• Concomitant use of postmenopausal hormone replacement therapy
• Use of any type of oral melatonin supplement in the past 30 days
• Acute/chronic heart failure with NYHA (New York Heart Association) score >II
• Uncontrolled orthostatic hypotension
• Recent acute myocardial infarction (3 to 6 months) or unstable angina.
• Acute/chronic respiratory failure.
• Diabetes mellitus with acute decompensation or uncontrolled hypoglycemia
• History of dementia (suspected by the GP environment and diagnosed).
• Shift-work and night-work

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanidad de Castilla y León

OTHER

Sponsor Role: collaborator

Ministerio de Ciencia e Innovación, Spain

OTHER_GOV

Sponsor Role: collaborator

Fundación General Universidad de Valladolid

OTHER

Sponsor Role: collaborator

University of Valladolid

OTHER

Sponsor Role: lead

Responsible Party

Diego Fernández Lázaro

Professor Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Faculty of Health Sciences, University of Valladolid Soria Campus

Soria, Soria, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Diego Fernández Lázaro, Professor; PhD

Role: CONTACT

diego.fernandez.lazaro@uva.es

+34 658073375

Cesar Ignacio Fernández Lázaro, Professor; PhD

Role: CONTACT

fernandezlazaro@usal.es

+34 975129185

Facility Contacts

Diego Fernández Lázaro, Vice Dean

Role: primary

diego.fernandez.lazaro@uva.es

658073375

References

Celorrio San Miguel AM, Cacharro LM, Santamaria G, Garrosa M, Celorrio San Miguel M, Roche E, Garrosa E, Fernandez-Lazaro D. Adjuvant melatonin therapy during exercise prescription in breast cancer survivors on physical and anthropometric parameters, quality of life, and hormonal response. A randomized controlled trial. Front Sports Act Living. 2025 Jun 23;7:1594733. doi: 10.3389/fspor.2025.1594733. eCollection 2025.

Reference Type: DERIVED

PMID: 40625889 (View on PubMed)

Other Identifiers

2024.08.12

Identifier Type: -

Identifier Source: org_study_id