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

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

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).

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.

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