Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy

Study Overview
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Brief Summary
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Breast cancer is the second most common cancer in the world, the most common in women, representing the leading cause of death in Brazil. The therapeutic approach for breast cancer includes surgery, radiotherapy, chemotherapy and endocrine therapy. Chemotherapy courses with side effects because the cytotoxic effects affect indistinctly neoplastic cells and normal cells. The cancer per se may promote disruption in circadian rhythm. Chemotherapy induces or enhances desynchronization of the sleep-wake cycle, which competes with impaired memory, mood, pain and poor quality of life. Melatonin is an attractive therapeutic option in this context. This neurohormone also has immunomodulatory, co-analgesic and anti-depressant properties. Additionally, the antioxidant properties of melatonin may decrease free radical formation, reducing damage to DNA. The objective is to assess the response to melatonin as a synchronizer of the sleep-wake rhythm, neuromodulator, and mieloprotetor genoprotetor in the effects induced by chemotherapy in women with breast cancer.

Detailed Description
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This is a randomized, double-blind clinical trial, parallel, placebo-controlled trial. Breast cancer women treated surgically and with indication for adjuvant chemotherapy, aged between 18 and 75 years will be included. Patients will be randomized to receive 20mg of melatonin or placebo at bedtime. Treatment will initiate seven days before the start of chemotherapy to three days after the first cycle, totaling ten days. The sleep-wake rhythm will be assessed by actigraphy, which use will precede three days to start treatment. We will also evaluate the sleep-wake cycle by sleep diary. Other parameters will be measured as depressive symptoms, pain threshold pressure, effect on platelets and white series, the pain response to conditioned stimuli and quality of life. Serum markers of neuroplasticity will be measured as the Derivate Nerve Factor Brain BDNF and S100 β. The icronucleus effect will quantified by cell material from the oral mucosa. We expect that the use of melatonin, as a competitor to chemotherapy and synchronizer, improves tolerance to adjuvant treatment of breast cancer chemotherapy adverse effects.

Official Title
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Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy: a Randomized, Double-blind, Placebo-controlled Trial.

Conditions
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Pain, Sleep Disorders, Circadian Rhythm, Depression, Genotoxicity

Intervention / Treatment
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* Drug: Melatonin 20 MG Oral Capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Diagnosed with breast cancer Indicated for the adjuvant treatment for breast cancer Between 18 years and 75 years Alphabetized Exclusion Criteria: Undergone chemotherapy or radiotherapy before inclusion in the study. Pregnant Epilepsy Brain Stroke Multiple sclerosis BMI above 45 kg / m 2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Melatonin<br>Melatonin 20 mg Oral Capsules, once a day at bedtime | Drug: Melatonin 20 MG Oral Capsule<br>* 1 capsule/day 1 hour before go to bed<br>* Other names: MTN;|
| Placebo Comparator: Placebo<br>Placebo Oral Capsules, once a day at bedtime | Drug: Placebo oral capsule<br>* 1 capsule/day 1 hour before go to bed<br>* Other names: PCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the response to melatonin as a sleep-wake rhythm synchronizer on the effects induced by chemotherapy in women with breast cancer. | Actigraphy to assess the circadian rhythm | 1 capsule of melatonin 20 mg or Placebo capsule, once a day, 1 hour before go to bed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep-wake rhytms, Melatonin, Breast cancer, Chemotherapy, Circadian rhythms