Efficacy and Safety of Melatonin PR and Clonazepam in Patients With REM Sleep Behavior Disorder in Parkinson Disease

NCT ID: NCT02789592

Last Updated: 2016-06-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2019-12-31

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).

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.

Conditions

REM Sleep Behavior Disorder; Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

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

Group Type: EXPERIMENTAL

Melatonin PR

Intervention Type: DRUG

For experimental treatment of RBD

Clonazepam

Intervention Type: DRUG

For experimental treatment of RBD

Melatonin PR placebo

Intervention Type: DRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Clonazepam placebo

Intervention Type: DRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

Interventions

Melatonin PR

For experimental treatment of RBD

Intervention Type: DRUG

Clonazepam

For experimental treatment of RBD

Intervention Type: DRUG

Melatonin PR placebo

Placebo pill manufactured to mask melatonin PR 2mg tablet

Intervention Type: DRUG

Clonazepam placebo

Placebo pill manufactured to mask clonazepam 0.5mg tablet

Intervention Type: DRUG

Other Intervention Names

Circadin; Rivotril; Placebo tablet of Melatonin PR; Placebo tablet of clonazepam

Eligibility 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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kuhnil Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

BS Jeon

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Beomseok Jeon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Countries

South Korea

Central Contacts

Beomseok Jeon, MD, PhD

Role: CONTACT

brain@snu.ac.kr

Chae Won Shin, MD, MSc

Role: CONTACT

chroma0202@gmail.com

References

Arnulf I. REM sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord. 2012 May;27(6):677-89. doi: 10.1002/mds.24957. Epub 2012 Mar 22.

Reference Type: BACKGROUND

PMID: 22447623 (View on PubMed)

Sixel-Doring F, Trautmann E, Mollenhauer B, Trenkwalder C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology. 2011 Sep 13;77(11):1048-54. doi: 10.1212/WNL.0b013e31822e560e. Epub 2011 Aug 10.

Reference Type: BACKGROUND

PMID: 21832215 (View on PubMed)

Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010 Dec;19(4):591-6. doi: 10.1111/j.1365-2869.2010.00848.x.

Reference Type: BACKGROUND

PMID: 20561180 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23886593 (View on PubMed)

Other Identifiers

H-1604-134-757

Identifier Type: -

Identifier Source: org_study_id