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Melatonin on Clock Genes in Parkinson's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04287543
Recruitment Status : Withdrawn (Due to the COVID-19 pandemic, we were unable to begin the study)
First Posted : February 27, 2020
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Blanca Miriam de Guadalupe Torres Mendoza, Instituto Mexicano del Seguro Social

Study Description
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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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Melatonin Drug: Placebos Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Melatonin Administration on the PER1 and BMAL1 Clock Genes in Patients With Parkinson's Disease
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


  5. 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.

  6. 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

  7. 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


Eligibility Criteria
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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04287543


Locations
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Mexico
Instituto Mexicano del Seguro Social
Guadalajara, Jalisco, Mexico, 44340
Sponsors and Collaborators
Instituto Mexicano del Seguro Social
Investigators
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Principal Investigator: Blanca M. Torres, PhD Instituto Mexicano del Seguro Social
More Information
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Additional Information:
INEGI  This link exits the ClinicalTrials.gov site

Publications:

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Responsible Party: Blanca Miriam de Guadalupe Torres Mendoza, Head of aging laboratory, Instituto Mexicano del Seguro Social
ClinicalTrials.gov Identifier: NCT04287543    
Other Study ID Numbers: R-2018-785-019
First Posted: February 27, 2020    Key Record Dates
Last Update Posted: August 4, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Blanca Miriam de Guadalupe Torres Mendoza, Instituto Mexicano del Seguro Social:
melatonin
clock genes
BMAL1 gene
PER1 gene
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
 Neurodegenerative Diseases
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants