Effect of Clonazepam on REM Sleep Behavior Disorder in Patients With Parkinsonism

Study Overview
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Brief Summary
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The purpose of this study is to determine whether clonazepam is effective and safe in the treatment of rapid eye movement behavior disorder (RBD) of patients with Parkinson's disease (PD).

Detailed Description
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RBD is one of the representative non-motor symptoms of PD and other synucleinopathies. 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. It decreased RBD symptoms completely in 55-79% and partially in 11-32% of patients. However, these results are based on open-label or descriptive studies. There has been no randomized placebo controlled study that evaluated the efficacy and safety of clonazepam for treating RBD.

Official Title
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Effect of Clonazepam on REM Sleep Behavior Disorder in Patients With Parkinsonism: a Prospective, Randomized, Double-blind and Placebo-controlled Trial

Conditions
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REM Sleep Behavior Disorder

Intervention / Treatment
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* Drug: Clonazepam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject was enrolled voluntarily and understood the contents of this clinical trial Subject was diagnosed as Parkinson disease (PD) or Parkinson's syndrome 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 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.)? Exclusion Criteria: Existence of cognitive decline hard to participate in the clinical trial Subject has confusion or visual hallucination in daytime Diagnosed as obstructive sleep apnea or severe snoring Previous clonazepam treatment within 4 weeks Current treatment with benzodiazepines at bedtime Alcoholics or drug abuser Lactating, pregnant, or possible pregnant Hypersensitivity to clonazepam or benzodiazepines 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

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clonazepam<br>Clonazepam 0.5 mg 1 Tablet by mouth, 1/day before sleeping for 4 weeks | Drug: Clonazepam<br>* For experimental treatment of RBD<br>* Other names: Rivotril;|
| Placebo Comparator: Placebo<br>Placebo 1 Tablet by mouth, 1/day before sleeping for 4 weeks | Drug: Placebo<br>* Placebo pill manufactured to mask clonazepam 0.5mg tablet<br>* Other names: Placebo tablet of Rivotril;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression-Severity scale (CGI-S) |  | Four weeks (plus or minus 3 days) | 
| Epworth Sleepiness Scale (ESS) |  | Four weeks (plus or minus 3 days) | 
| Parkinson Disease Sleep Scale (PDSS) |  | Four weeks (plus or minus 3 days) | 
| Montreal Cognitive Assessment (MoCA) |  | Four weeks (plus or minus 3 days) | 
| Unified Parkinson's Disease Rating Scale (UPDRS) |  | Four weeks (plus or minus 3 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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REM Sleep Behavior Disorder, Parkinson Disease, Placebos, Randomized Controlled Trial, Double-Blind Method, Clinical Trial