Clinical trial NCT03205033: Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy
Official title: Melatonin as a Circadian Clock Regulator, Neuromodulator and Myelo-protector in Adjuvant Breast Cancer Chemotherapy: a Randomized, Double-blind, Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sleep Disorders, Circadian Rhythm
Depression
Genotoxicity
Pain
Keywords: Melatonin
Breast cancer
Chemotherapy
Sleep-wake rhytms
Circadian rhythms
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the response to melatonin as a sleep-wake rhythm synchronizer on the effects induced by chemotherapy in women with breast cancer.
timeFrame: 1 capsule of melatonin 20 mg or Placebo capsule, once a day, 1 hour before go to bed
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Hospital de Clínicas de Porto Alegre
name: Wolnei Caumo, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palmer ACS, Souza A, Dos Santos VS, Cavalheiro JAC, Schuh F, Zucatto AE, Biazus JV, Torres ILDS, Fregni F, Caumo W. The Effects of Melatonin on the Descending Pain Inhibitory System and Neural Plasticity Markers in Breast Cancer Patients Receiving Chemotherapy: Randomized, Double-Blinded, Placebo-Controlled Trial. Front Pharmacol. 2019 Nov 22;10:1382. doi: 10.3389/fphar.2019.01382. eCollection 2019.