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Efficacy and Safety of Melatonin PR and Clonazepam in Patients With REM Sleep Behavior Disorder in Parkinson 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: NCT02789592
Recruitment Status : Unknown
Verified June 2016 by BS Jeon, Seoul National University Hospital.
Recruitment status was:  Not yet recruiting
First Posted : June 3, 2016
Last Update Posted : June 3, 2016
Sponsor:
Collaborator:
Kuhnil Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
BS Jeon, Seoul National University Hospital

Study Description
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Brief Summary:
The purpose of this study is to determine whether melatonin prolonged-release (PR) and clonazepam are effective and safe in the treatment of rapid eye movement behavior disorder (RBD) of patients with Parkinson's disease (PD).

Condition or disease Intervention/treatment Phase
REM Sleep Behavior Disorder Parkinson Disease Drug: Melatonin PR Drug: Clonazepam Drug: Melatonin PR placebo Drug: Clonazepam placebo Phase 2

Detailed Description:

RBD is one of the representative non-motor symptoms of PD. Patients with RBD show dream-enacting behaviors such as punching, kicking, singing, screaming, or somnambulism. These can interfere in sleep quality and increase the risk of falling down from the bed and physical injuries of both the patient and sleep partner. Therefore, qualities of life of the patient and sleep partner are negatively influenced by presence of RBD.

Clonazepam has been used for treatment of choice of RBD. However, the efficacy of clonazepam is not proven in the clinical trial. Clonazepam has several side effects that could be problematic in PD patients such as increasing fall-down risk, daytime somnolence, and cognitive decline. Melatonin is a second-line treatment option for RBD, but there has been only one randomized crossover trial that evaluated the efficacy of melatonin on RBD. Finally, there has been no study that evaluate and compare the efficacy and safety of melatonin and clonazepam for treatment of RBD.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind, Double-Dummy, Crossover Study to Evaluate the Efficacy and Safety of Prolonged-Release Melatonin and Clonazepam in Patients With Rapid Eye Movement (REM) Sleep Behavior Disorder in Parkinson Disease
Study Start Date : July 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Group 1
Phase 1: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam
Experimental: Group 2
Phase 1: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam
Experimental: Group 3
Phase 1: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam
Experimental: Group 4
Phase 1: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam
Experimental: Group 5
Phase 1: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam
Experimental: Group 6
Phase 1: Melatonin PR placebo 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 2: Clonazepam 0.5 mg 1 tablet+Melatonin PR placebo 1 tablet, 1/day before sleeping for 4 weeks Phase 3: Melatonin PR 2 mg 1 tablet+Clonazepam placebo 1 tablet, 1/day before sleeping for 4 weeks
 Drug: Melatonin PR
For experimental treatment of RBD
Other Name: Circadin

Drug: Clonazepam
For experimental treatment of RBD
Other Name: Rivotril

Drug: Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
Other Name: Placebo tablet of Melatonin PR

Drug: Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet
Other Name: Placebo tablet of clonazepam


Outcome Measures
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Primary Outcome Measures :
  1. Clinical Global Impression-Improvement scale (CGI-I) [ Time Frame: Four weeks (plus or minus 3 days) ]
    Clinician assessed rating scale of clinical improvement or worsening relative to a baseline state, scored as 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.


Secondary Outcome Measures :
  1. Mean change of the Clinical Global Impression-Severity scale (CGI-S) [ Time Frame: Four weeks (plus or minus 3 days) ]
  2. Patient Global Impression-Improvement scale (PGI-I) [ Time Frame: Four weeks (plus or minus 3 days) ]
  3. Mean change of the Patient Global Impression-Severity scale (PGI-S) [ Time Frame: Four weeks (plus or minus 3 days) ]
  4. modified RBD Questionnaire-HongKong (mRBDQ-HK) [ Time Frame: Four weeks (plus or minus 3 days) ]
  5. Mean change of the Epworth Sleepiness Scale (ESS) [ Time Frame: Four weeks (plus or minus 3 days) ]
  6. Mean change of the Parkinson Disease Sleep Scale (PDSS) [ Time Frame: Four weeks (plus or minus 3 days) ]
  7. Mean change of the Montreal Cognitive Assessment (MoCA) [ Time Frame: Four weeks (plus or minus 3 days) ]
  8. Mean change of the Unified Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: Four weeks (plus or minus 3 days) ]
  9. Sleep diary [ Time Frame: Four weeks (plus or minus 3 days) ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject was enrolled voluntarily and understood the contents of this clinical trial
  • Subject was diagnosed as Parkinson disease (PD)
  • Hoehn and Yahr (H&Y) stage 1, 2, or 3
  • Existence of caregivers who can provide a information about symptoms of rapid eye movement sleep disorder (RBD) of the participant
  • RBD frequency is one or more per week
  • Existence of RBD by answering "yes" to the question (RBD-1Q): "Have you ever been told, or suspected yourself, that you seem to 'act out your dreams' while asleep (for example, punching, flailing your arms in the air, making running movements, etc.)?"
  • Good compliance for reporting PGI scores and sleep diary

Exclusion Criteria:

  • Existence of cognitive decline hard to participate in the clinical trial
  • Hypersensitivity to melatonin or clonazepam
  • Previous melatonin or clonazepam treatment within 1 month
  • Changing anti-parkinsonian medications within 1 month
  • Current treatment with sedatives or hypnotics at bedtime
  • Diagnosed as epilepsy or current treatment with anti-epileptic drugs
  • Severe trauma history due to RBD
  • Lactating, pregnant, or possible pregnant
  • Subject has confusion or visual hallucination in daytime
  • Diagnosed as obstructive sleep apnea or severe snoring
  • Diagnosed as other parasomnia
  • Presence of severe psychiatric illness
  • Alcoholics or drug abuser
  • Myasthenia gravis
  • Acute narrow-angle glaucoma
  • Prior participation to other clinical trials within 3 months
  • Presence of severe comorbidities or a cancer
  • Existence of illness or problems which makes difficult to be enrolled to this trial judged by clinicians
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): NCT02789592


Contacts
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Contact: Beomseok Jeon, MD, PhD brain@snu.ac.kr
Contact: Chae Won Shin, MD, MSc chroma0202@gmail.com

Locations
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Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Sponsors and Collaborators
Seoul National University Hospital
Kuhnil Pharmaceutical Co., Ltd.
Investigators
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Principal Investigator: Beomseok Jeon, MD, PhD Seoul National University Hospital
More Information
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Publications:
Schenck CH, Montplaisir JY, Frauscher B, Hogl B, Gagnon JF, Postuma R, Sonka K, Jennum P, Partinen M, Arnulf I, Cochen de Cock V, Dauvilliers Y, Luppi PH, Heidbreder A, Mayer G, Sixel-Doring F, Trenkwalder C, Unger M, Young P, Wing YK, Ferini-Strambi L, Ferri R, Plazzi G, Zucconi M, Inoue Y, Iranzo A, Santamaria J, Bassetti C, Moller JC, Boeve BF, Lai YY, Pavlova M, Saper C, Schmidt P, Siegel JM, Singer C, St Louis E, Videnovic A, Oertel W. Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. Sleep Med. 2013 Aug;14(8):795-806. doi: 10.1016/j.sleep.2013.02.016. Epub 2013 Jul 22. Erratum In: Sleep Med. 2014 Jan;15(1):157.

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Responsible Party: BS Jeon, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT02789592    
Other Study ID Numbers: H-1604-134-757
First Posted: June 3, 2016    Key Record Dates
Last Update Posted: June 3, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by BS Jeon, Seoul National University Hospital:
REM Sleep Behavior Disorder
Parkinson Disease
Randomized Controlled Trial
 Clinical Trial
Melatonin
Clonazepam
Additional relevant MeSH terms:
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Parkinson Disease
REM Sleep Behavior Disorder
Disease
Mental Disorders
Pathologic Processes
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
REM Sleep Parasomnias
 Parasomnias
Sleep Wake Disorders
Clonazepam
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants
Anticonvulsants
GABA Modulators
GABA Agents
Neurotransmitter Agents