Clinical Trials/NCT02789592

NCT02789592

Unknown

Phase 2

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

Seoul National University Hospital1 site in 1 country30 target enrollmentStarted: July 2016Last updated: June 3, 2016

ConditionsREM Sleep Behavior Disorder Parkinson Disease

InterventionsClonazepam placebo Melatonin PR Clonazepam Melatonin PR placebo

DrugsMelatonin PR Clonazepam Melatonin PR placebo Clonazepam placebo

Overview

Phase: Phase 2
Sponsor: Seoul National University Hospital
Enrollment: 30
Locations: 1
Primary Endpoint: Clinical Global Impression-Improvement scale (CGI-I)

Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Overview

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.

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Crossover
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages: 30 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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

Arms & Interventions

Group 1

Experimental

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

Intervention: Clonazepam placebo (Drug)

Group 1

Experimental

Intervention: Melatonin PR (Drug)

Group 1

Experimental

Intervention: Clonazepam (Drug)

Group 1

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 2

Experimental

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

Intervention: Melatonin PR (Drug)

Group 2

Experimental

Intervention: Clonazepam (Drug)

Group 2

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 2

Experimental

Intervention: Clonazepam placebo (Drug)

Group 3

Experimental

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

Intervention: Melatonin PR (Drug)

Group 3

Experimental

Intervention: Clonazepam (Drug)

Group 3

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 3

Experimental

Intervention: Clonazepam placebo (Drug)

Group 4

Experimental

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

Intervention: Melatonin PR (Drug)

Group 4

Experimental

Intervention: Clonazepam (Drug)

Group 4

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 4

Experimental

Intervention: Clonazepam placebo (Drug)

Group 5

Experimental

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

Intervention: Melatonin PR (Drug)

Group 5

Experimental

Intervention: Clonazepam (Drug)

Group 5

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 5

Experimental

Intervention: Clonazepam placebo (Drug)

Group 6

Experimental

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

Intervention: Melatonin PR (Drug)

Group 6

Experimental

Intervention: Clonazepam (Drug)

Group 6

Experimental

Intervention: Melatonin PR placebo (Drug)

Group 6

Experimental

Intervention: Clonazepam placebo (Drug)

Outcomes

Primary Outcomes

Clinical Global Impression-Improvement scale (CGI-I)

Time Frame: Four weeks (plus or minus 3 days)

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.

Secondary Outcomes

Mean change of the Clinical Global Impression-Severity scale (CGI-S)(Four weeks (plus or minus 3 days))
Patient Global Impression-Improvement scale (PGI-I)(Four weeks (plus or minus 3 days))
Mean change of the Patient Global Impression-Severity scale (PGI-S)(Four weeks (plus or minus 3 days))
modified RBD Questionnaire-HongKong (mRBDQ-HK)(Four weeks (plus or minus 3 days))
Mean change of the Epworth Sleepiness Scale (ESS)(Four weeks (plus or minus 3 days))
Mean change of the Parkinson Disease Sleep Scale (PDSS)(Four weeks (plus or minus 3 days))
Mean change of the Montreal Cognitive Assessment (MoCA)(Four weeks (plus or minus 3 days))
Mean change of the Unified Parkinson's Disease Rating Scale (UPDRS)(Four weeks (plus or minus 3 days))
Sleep diary(Four weeks (plus or minus 3 days))

Investigators

Sponsor

Seoul National University Hospital

Sponsor Class

Other

Responsible Party

Principal Investigator

BS Jeon

Professor

Seoul National University Hospital

Study Sites (1)

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