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

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02789592
• Other study ID #: H-1604-134-757
• Status: Not yet recruiting
• Phase: Phase 2
• First received: May 31, 2016
• Last updated: June 2, 2016
• Start date: July 2016
• Est. completion date: December 2019

Study information

• Verified date: June 2016
• Source: Seoul National University Hospital
• Contact: Beomseok Jeon, MD, PhD
• Email: brain[@]snu.ac.kr
• Is FDA regulated: No
• Health authority: South Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mental Disorders
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

Drug:
• Melatonin PR
For experimental treatment of RBD
• Clonazepam
For experimental treatment of RBD
• Melatonin PR placebo
Placebo pill manufactured to mask melatonin PR 2mg tablet
• Clonazepam placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Kuhnil Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (4)

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. Review. — View Citation

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. — View Citation

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-Döring 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, Möller 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. — View Citation

Sixel-Döring 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Global Impression-Improvement scale (CGI-I)	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.	Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Clinical Global Impression-Severity scale (CGI-S)		Four weeks (plus or minus 3 days)	No
Secondary	Patient Global Impression-Improvement scale (PGI-I)		Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Patient Global Impression-Severity scale (PGI-S)		Four weeks (plus or minus 3 days)	No
Secondary	modified RBD Questionnaire-HongKong (mRBDQ-HK)		Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Epworth Sleepiness Scale (ESS)		Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Parkinson Disease Sleep Scale (PDSS)		Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Montreal Cognitive Assessment (MoCA)		Four weeks (plus or minus 3 days)	No
Secondary	Mean change of the Unified Parkinson's Disease Rating Scale (UPDRS)		Four weeks (plus or minus 3 days)	No
Secondary	Sleep diary		Four weeks (plus or minus 3 days)	No