NCT02789592

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2016

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 31, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 3, 2016

Completed
28 days until next milestone

Study Start

First participant enrolled

July 1, 2016

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

June 3, 2016

Status Verified

June 1, 2016

Enrollment Period

3.4 years

First QC Date

May 31, 2016

Last Update Submit

June 2, 2016

Conditions

REM Sleep Behavior DisorderParkinson Disease

Keywords

REM Sleep Behavior DisorderParkinson DiseaseRandomized Controlled TrialClinical TrialMelatoninClonazepam

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (9)

  • 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)

  • +4 more secondary outcomes

Study Arms (6)

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

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

Drug: Melatonin PRDrug: ClonazepamDrug: Melatonin PR placeboDrug: Clonazepam placebo

Interventions

Melatonin PRDRUG

For experimental treatment of RBD

Also known as: Circadin
Group 1Group 2Group 3Group 4Group 5Group 6
ClonazepamDRUG

For experimental treatment of RBD

Also known as: Rivotril
Group 1Group 2Group 3Group 4Group 5Group 6
Melatonin PR placeboDRUG

Placebo pill manufactured to mask melatonin PR 2mg tablet

Also known as: Placebo tablet of Melatonin PR
Group 1Group 2Group 3Group 4Group 5Group 6
Clonazepam placeboDRUG

Placebo pill manufactured to mask clonazepam 0.5mg tablet

Also known as: Placebo tablet of clonazepam
Group 1Group 2Group 3Group 4Group 5Group 6

Eligibility Criteria

Age30 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

Location

Related 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.

    PMID: 22447623BACKGROUND

  • 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.

    PMID: 21832215BACKGROUND

  • 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.

    PMID: 20561180BACKGROUND

  • 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.

    PMID: 23886593BACKGROUND

MeSH Terms

Conditions

REM Sleep Behavior DisorderParkinson Disease

Interventions

MelatoninClonazepam

Condition Hierarchy (Ancestors)

REM Sleep ParasomniasParasomniasSleep Wake DisordersNervous System DiseasesMental DisordersParkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative Diseases

Intervention Hierarchy (Ancestors)

TryptaminesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHormonesHormones, Hormone Substitutes, and Hormone AntagonistsBenzodiazepinonesBenzodiazepinesBenzazepines

Study Officials

  • Beomseok Jeon, MD, PhD

    Seoul National University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Beomseok Jeon, MD, PhD

CONTACT

brain@snu.ac.kr

Chae Won Shin, MD, MSc

CONTACT

chroma0202@gmail.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

May 31, 2016

First Posted

June 3, 2016

Study Start

July 1, 2016

Primary Completion

December 1, 2019

Study Completion

December 1, 2019

Last Updated

June 3, 2016

Record last verified: 2016-06

Locations

KR(1)