Melatonin Supplementation and Exercise Program in Breast Cancer Women

NCT06696378 | Recruiting DMC

• 1 other identifier: 2024.08.12
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Keywords

Brear Cancer; Melatonin; quality of life; physical performance; health biomarkers; antioxidant capacity; anthropometrics parameters; Exerkins

Outcome Measures

Primary Outcomes (2)

• Irisin

  Exerkin secreted primarily by skeletal muscle in response to exercise

  first day of study and after 60 days of supplementation (end of study)

• Sestrin-2

  Exerkin a highly conserved stress-responsive protein, can be triggered by various noxious stimuli, such as hypoxia, DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation.

  first day of study and after 60 days of supplementation (end of study)

Secondary Outcomes (13)

• BAP

  first day of study and after 60 days of supplementation (end of study)

• d-ROMs

  first day of study and after 60 days of supplementation (end of study)

• World Health Organization Quality of Life - BREF (WHOQOL-BREF)

  first day of study and after 60 days of supplementation (end of study)

• Creatine kinase (CK)

  first day of study and after 60 days of supplementation (end of study)

• Lactate dehydrogenase (LDH)

  first day of study and after 60 days of supplementation (end of study)

Study Arms (2)

Melatonin supplementation group

EXPERIMENTAL

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

Dietary Supplement: Melatonin 6 mg

Placebo supplementation group

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Melatonin 6 mg 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).

Melatonin supplementation group

Placebo 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.

Placebo supplementation group

Eligibility Criteria

• Age: 60 Years - 80 Years
• Gender Eligibility Details: Older women who have suffered from breast cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Valladolid: lead
• Sanidad de Castilla y León: collaborator
• Ministerio de Ciencia e Innovación, Spain: collaborator
• Fundación General Universidad de Valladolid: collaborator

Study Sites (1)

Faculty of Health Sciences, University of Valladolid Soria Campus

Soria, Soria, 42004, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 40625889 DERIVED

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Diego Fernández Lázaro, Professor; PhD

CONTACT

+34 658073375; diego.fernandez.lazaro@uva.es

Cesar Ignacio Fernández Lázaro, Professor; PhD

CONTACT

+34 975129185; fernandezlazaro@usal.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double (Investigator, Participants)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Doctor

Model Details: Parallel group placebo-controlled randomized clinical trial

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: November 20, 2024
• Study Start: January 15, 2025
• Primary Completion: December 20, 2025
• Study Completion: May 1, 2026
• Last Updated: November 20, 2024

Record last verified: 2024-08

Locations

ES (1)