Clinical trial NCT02789592: Efficacy and Safety of Melatonin PR and Clonazepam in Patients With REM Sleep Behavior Disorder in Parkinson Disease
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: REM Sleep Behavior Disorder
Parkinson Disease
Keywords: REM Sleep Behavior Disorder
Parkinson Disease
Randomized Controlled Trial
Clinical Trial
Melatonin
Clonazepam
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Kuhnil Pharmaceutical Co., Ltd.
First posted: 2016-06-03
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical Global Impression-Improvement scale (CGI-I)
timeFrame: Four weeks (plus or minus 3 days)
Secondary outcomes:
measure: Mean change of the Clinical Global Impression-Severity scale (CGI-S)
timeFrame: Four weeks (plus or minus 3 days)
measure: Patient Global Impression-Improvement scale (PGI-I)
timeFrame: Four weeks (plus or minus 3 days)
measure: Mean change of the Patient Global Impression-Severity scale (PGI-S)
timeFrame: Four weeks (plus or minus 3 days)
measure: modified RBD Questionnaire-HongKong (mRBDQ-HK)
timeFrame: Four weeks (plus or minus 3 days)
measure: Mean change of the Epworth Sleepiness Scale (ESS)
timeFrame: Four weeks (plus or minus 3 days)
measure: Mean change of the Parkinson Disease Sleep Scale (PDSS)
timeFrame: Four weeks (plus or minus 3 days)
measure: Mean change of the Montreal Cognitive Assessment (MoCA)
timeFrame: Four weeks (plus or minus 3 days)
measure: Mean change of the Unified Parkinson's Disease Rating Scale (UPDRS)
timeFrame: Four weeks (plus or minus 3 days)
measure: Sleep diary
timeFrame: Four weeks (plus or minus 3 days)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Beomseok Jeon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.
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-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.