Clinical trial NCT04287543: Melatonin on Clock Genes in Parkinson's Disease
Official title: Effect of Melatonin Administration on the PER1 and BMAL1 Clock Genes in Patients With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Parkinson Disease
Keywords: melatonin
clock genes
BMAL1 gene
PER1 gene
Lead sponsor: Instituto Mexicano del Seguro Social
Sponsor class: OTHER_GOV
First posted: 2020-02-27
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinson's disease (PD) is the second most important neurodegenerative disease that affects about 2% of the population over 60 years of age. About 40% of the Mexican population with PD suffer from sleep disorders, which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. Melatonin is a hormone produced by the pineal gland that regulates the sleep-wake cycle, at pharmacological doses, it is used to decrease sleep disorders; it is suggested that is used could also normalize the levels of the clock genes expression. In rats with PD, a decrease in clock genes levels has been observed, which are restored by administering melatonin. The aim of the study is to evaluate the effect of melatonin on the expression of the PER1 and BMAL1 clock genes in patients with PD during 12 months. A controlled, double-blind, randomized clinical trial will be carried out in patients with a diagnosis of PD. A survey will be applied in order to know the course of the disease and two more tests to rule out some sleep disorder, at the beginning of the study, at the 6th month and at the 12th month. A blood sample (approximately 15 ml) will be taken every 3 months for a year. By random assignment, the participant will be given Melatonin or placebo, which should be taken every day in the morning and evening after meals for one year.

Detailed description: A controlled, double-blind, randomized clinical trial will be carried out in 58 patients with a diagnosis of PD. Twenty-nine patients will receive Melatonin and 29 placebo. A blood sample will be taken to determine the expression levels of the PER1 and BMAL1 clock genes by a real-time quantitative polymerase chain reaction (RT-qPCR), and as secondary variables, to determine the activity of the mitochondrial complex 1, the levels of malondialdehyde (MDA) and 4-hydroxyalkene (4-HDA) and the production of nitric oxide will be quantified by spectrophotometric methods. The SCOPA-Sleep and EPWORTH questionnaires will be applied to assess sleep. To evaluate the clinical evolution of PD in each patient, the UPDRS scale will be used. It will be given the assigned treatment, with the printed patient code. They will be supplemented with 50 mg of Melatonin at a dose of 25 mg orally every 12 hours for 12 months. The double-blind of the medication for this study will be maintained by the use of gels identical to the Melatonin supplement. The blind's break will only be authorized in case of emergency events that require it, and the date, time and reason for the break should be noted. It will be given a follow-up diary, and the patient will be explained how they should take the treatment and that they should record the date and time of administration, the description of adverse events that may occur, raising the patient's awareness that It is important to keep the diary and take it at each appointment to assess the attachment to treatment. Concerning the medications that patients ingest, before entering the protocol, it will be indicated to follow their usual administration. Finally, the patient will be instructed to schedule their appointment 3,6, 9 and 12 months later of starting treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with diagnosis of PD in stages 1-3 of the classification by stages of Hoehn \& Yahr
* Go with a companion to the appointments
* Patients who agree to participate in the study and sign the Informed Consent letter

Exclusion Criteria:

* Patients with movement disorder other than PD
* Prior pallidotomy, thalamotomy or deep brain stimulation
* Pregnant
* Patients who consume alcohol or coffee
* Patients who consume an antioxidant supplement

Primary outcomes:
measure: Expression levels of clock genes
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
Secondary outcomes:
measure: SCOPA-Sleep scale
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Epworth scale
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Progression of PD
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Anxiety
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Depression
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Activity of the mitochondrial complex 1
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
measure: Oxidative stress
timeFrame: Change from baseline at third, sixth, ninth and twelfth month
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Instituto Mexicano del Seguro Social
state: Jalisco
Study officials:
affiliation: Instituto Mexicano del Seguro Social
name: Blanca M. Torres, PhD
role: PRINCIPAL_INVESTIGATOR
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