Melatonin Supplementation and Exercise Program in Breast Cancer Women

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age60-80
SponsorUniversity of Valladolid

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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).

  • Placebo

    Other intervention

    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.

Treatment groups

120 Participants
are divided into 2 treatment groups
Group A: Melatonin supplementation groupExperimental treatment 1 intervention
Group B: Placebo supplementation groupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Irisin

Exerkin secreted primarily by skeletal muscle in response to exercise

Time frame
first day of study and after 60 days of supplementation (end of study)
2

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.

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

Secondary outcomes

1

BAP

biological antioxidant potential (BAP) test to estimate antioxidant capacity by measuring the blood concentration of antioxidants

Time frame
first day of study and after 60 days of supplementation (end of study)
2

d-ROMs

diacron reactive oxygen metabolites (d-ROMs) pro-oxidant state of a biological sample, measures hydroperoxides

Time frame
first day of study and after 60 days of supplementation (end of study)
3

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

a self-report questionnaire which assesses 4 domains of quality of life (QOL): physical health, psychological health, social relationships, and environment

Time frame
first day of study and after 60 days of supplementation (end of study)
4

Creatine kinase (CK)

CK is an enzyme expressed by various tissues and cell types; markers of muscle damage

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

Other outcomes

Sponsors and contacts

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University of Valladolid

Lead sponsor

Sanidad de Castilla y León

Collaborator

Ministerio de Ciencia e Innovación, Spain

Collaborator

Fundación General Universidad de Valladolid

Collaborator