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

Phase 2

Completed

• Conditions: Sleep Disorders, Circadian Rhythm; Genotoxicity; Depression; Pain
• Interventions: Drug: Placebo oral capsule; Drug: Melatonin 20 MG Oral Capsule

• Registration Number: NCT03205033
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-01
• Status Verified: 2017-01
• Primary Completion: 2017-01
• Study Completion: 2017-01
• Study First Submitted: 2017-06-28
• Study First Submitted QC: 2017-06-28
• Last Update Submitted: 2017-06-28
• Study First Posted: 2017-07-02
• Last Update Posted: 2017-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral capsule	Placebo Oral Capsules, once a day at bedtime
Melatonin	Melatonin 20 MG Oral Capsule	Melatonin 20 mg Oral Capsules, once a day at bedtime

Primary Outcome Measures

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