Melatonin on Clock Genes in Parkinson's Disease

July 31, 2020 updated by: Blanca Miriam de Guadalupe Torres Mendoza, Instituto Mexicano del Seguro Social

Effect of Melatonin Administration on the PER1 and BMAL1 Clock Genes in Patients With Parkinson's Disease

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44340
        • Instituto Mexicano del Seguro Social

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Melatonin group
Patients with PD who will receive 25 mg of melatonin gel at 12 hours a day and half an hour before sleeping for 12 months
Drug: Melatonin
25 mg of melatonin gel at noon and 25 mg of melatonin gel 30 minutes before sleeping for 12 months
Placebo Comparator: Placebo group
Patients with PD who will receive 25 mg of placebo gel at 12 hours a day and half an hour before sleeping for 12 months
Drug: Placebos
25 mg of placebo gel at noon and 25 mg of placebo gel 30 minutes before sleeping for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expression levels of clock genes
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
Relative ratio of messenger ribonucleic acid (mRNA) expression of PER1 and BMAL1 genes corresponding to a control (GAPDH) for each sample, measured by an RT-qPCR.
Change from baseline at third, sixth, ninth and twelfth month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SCOPA-Sleep scale
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
It is a specific instrument for the evaluation of sleep disorders in patients with PD. It is self-applicable and consists of two subscales; the first assess nighttime sleep and the second daytime sleepiness during the last month. The score greater than seven of five points respectively indicates abnormal sleepiness. Additionally, the SCOPA-Sleep scale has a question of global sleep evaluation.
Change from baseline at third, sixth, ninth and twelfth month
Epworth scale
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
Is an eight-item self-applicable instrument developed to assess the propensity to fall asleep in eight situations, mostly monotonous. A total score of less than 10 was considered normal, 10-12 as indicative of marginal drowsiness and above 12 suggestive of excessive drowsiness.
Change from baseline at third, sixth, ninth and twelfth month
Progression of PD
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
For the longitudinal follow-up of the PD course, the Unified Parkinson's Disease Rating Scale (UPDRS) will be applied through an interview. The scale is composed by four parts: mental, behavioral and mood; activities of daily living; motor evaluation; and motor complications. The scoring range is from 0 to 199, where "199" represents total disability and "0" without disability.
Change from baseline at third, sixth, ninth and twelfth month
Anxiety
Time Frame: Change from baseline at third, sixth, ninth and twelfth month

To assess the severity of a person's anxiety symptoms and discriminate between anxiety and depression symptoms the Beck anxiety inventory will be use.

The rating is made through a likert scale of 0 to 3, where 0 means absence of the symptom and 3 maximum severity. The total score is obtained from the sum of the 21 reagents, 0 is the minimum and 63 is the maximum. In the Mexican population, a score of 0-5 points will be minimal anxiety, 6-15 mild anxiety, 16-30 moderate anxiety and 31-63 severe anxiety.
Change from baseline at third, sixth, ninth and twelfth month
Depression
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
To evaluate the severity of depression symptoms the Beck's depression inventory will be use. The rating is made through a likert scale of 0 to 3, where 0 means absence of the symptom and 3 maximum severity. The total score is obtained from the sum of the 21 reagents, 0 is the minimum and 63 is the maximum. In the Mexican population, a score of 0-9 points will be considered normal, 10-16 mild depression, 17-29 moderate depression, and 30-63 severe depression.
Change from baseline at third, sixth, ninth and twelfth month
Activity of the mitochondrial complex 1
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
To measure the mitochondrial complex I, a spectrophotometric assay will be used, it measures the oxidation of rotenone-sensitive nicotinamide-adenine dinucleotide (NADH) at 340 nm in mitochondria-enriched fractions
Change from baseline at third, sixth, ninth and twelfth month
Oxidative stress
Time Frame: Change from baseline at third, sixth, ninth and twelfth month
Products of nitric oxide metabolism and products of lipoperoxidation such as malondialdehyde and 4-hydroxyalkene by spectrophotometry will be measured
Change from baseline at third, sixth, ninth and twelfth month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Mexicano del Seguro Social

Investigators

  • Principal Investigator: Blanca M. Torres, PhD, Instituto Mexicano del Seguro Social

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 1, 2021

Primary Completion (Anticipated)

July 1, 2022

Study Completion (Anticipated)

August 1, 2022

Study Registration Dates

First Submitted

February 21, 2020

First Submitted That Met QC Criteria

February 25, 2020

First Posted (Actual)

February 27, 2020

Study Record Updates

Last Update Posted (Actual)

August 4, 2020

Last Update Submitted That Met QC Criteria

July 31, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-2018-785-019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

It is planned to inform the patient individually about their results; if the results are favorable it will be considered to apply them to the Clinical of Movement Disorders patients. All data will be published in an article.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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