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Melatonin on Clock Genes in Parkinson's Disease

Primary Purpose

Parkinson Disease

Status

Withdrawn

Phase

Phase 2

Locations

Mexico

Study Type

Interventional

Intervention

Melatonin

Placebos

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring melatonin, clock genes, BMAL1 gene, PER1 gene

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Instituto Mexicano del Seguro Social

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Melatonin group

Placebo group

Arm Description

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

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

Outcomes

Primary Outcome Measures

Expression levels of clock genes

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.

Secondary Outcome Measures

SCOPA-Sleep scale

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.

Epworth scale

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.

Progression of PD

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.

Anxiety

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.

Depression

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.

Activity of the mitochondrial complex 1

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

Oxidative stress

Products of nitric oxide metabolism and products of lipoperoxidation such as malondialdehyde and 4-hydroxyalkene by spectrophotometry will be measured

Full Information

NCT ID

NCT04287543

First Posted

February 21, 2020

Last Updated

July 31, 2020

Sponsor

Instituto Mexicano del Seguro Social

1. Study Identification

Unique Protocol Identification Number

NCT04287543

Brief Title

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Due to the COVID-19 pandemic, we were unable to begin the study

Study Start Date

May 2021 (Anticipated)

Primary Completion Date

July 2022 (Anticipated)

Study Completion Date

August 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Instituto Mexicano del Seguro Social

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

Keywords

melatonin, clock genes, BMAL1 gene, PER1 gene

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Melatonin group

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Melatonin

Intervention Description

25 mg of melatonin gel at noon and 25 mg of melatonin gel 30 minutes before sleeping for 12 months

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

25 mg of placebo gel at noon and 25 mg of placebo gel 30 minutes before sleeping for 12 months

Primary Outcome Measure Information:

Title

Expression levels of clock genes

Description

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.

Time Frame