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

REM Sleep Behavior Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02312908
• Other study ID #: 14172EuiYakAn178
• Status: Completed
• Phase: Phase 2
• First received: December 5, 2014
• Last updated: April 13, 2016
• Start date: March 2015
• Est. completion date: March 2016

Study information

• Verified date: April 2016
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mental Disorders
• Parkinsonian Disorders
• REM Sleep Behavior Disorder

Intervention

Drug:
• Clonazepam
For experimental treatment of RBD
• Placebo
Placebo pill manufactured to mask clonazepam 0.5mg tablet

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Ministry of Food and Drug Safety, Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

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. Review. — View Citation

Aurora RN, Zak RS, Maganti RK, Auerbach SH, Casey KR, Chowdhuri S, Karippot A, Ramar K, Kristo DA, Morgenthaler TI; Standards of Practice Committee; American Academy of Sleep Medicine. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010 Feb 15;6(1):85-95. Erratum in: J Clin Sleep Med. 2010 Apr 15;6(2):table of contents. — View Citation

De Cock VC, Vidailhet M, Arnulf I. Sleep disturbances in patients with parkinsonism. Nat Clin Pract Neurol. 2008 May;4(5):254-66. doi: 10.1038/ncpneuro0775. Epub 2008 Apr 8. Review. — View Citation

Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology. 2006 Sep 12;67(5):742-7. — View Citation

Howell MJ, Arneson PA, Schenck CH. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011 Dec 15;7(6):639-644A. doi: 10.5664/jcsm.1470. — View 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. — View Citation

Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000 Feb;123 ( Pt 2):331-9. — View Citation

Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, Oertel W, Ju YE, Puligheddu M, Jennum P, Pelletier A, Wolfson C, Leu-Semenescu S, Frauscher B, Miyamoto M, Cochen De Cock V, Unger MM, Stiasny-Kolster K, Fantini ML, Montplaisir JY. A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord. 2012 Jun;27(7):913-6. doi: 10.1002/mds.25037. Epub 2012 May 30. — View Citation

Postuma RB, Bertrand JA, Montplaisir J, Desjardins C, Vendette M, Rios Romenets S, Panisset M, Gagnon JF. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: a prospective study. Mov Disord. 2012 May;27(6):720-6. doi: 10.1002/mds.24939. Epub 2012 Feb 9. — View Citation

Schenck CH, Hurwitz TD, Mahowald MW. Symposium: Normal and abnormal REM sleep regulation: REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature. J Sleep Res. 1993 Dec;2(4):224-231. — View Citation

Sixel-Döring 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Clinical Global Impression-Severity scale (CGI-S)		Four weeks (plus or minus 3 days)	No
Secondary	Epworth Sleepiness Scale (ESS)		Four weeks (plus or minus 3 days)	No
Secondary	Parkinson Disease Sleep Scale (PDSS)		Four weeks (plus or minus 3 days)	No
Secondary	Montreal Cognitive Assessment (MoCA)		Four weeks (plus or minus 3 days)	No
Secondary	Unified Parkinson's Disease Rating Scale (UPDRS)		Four weeks (plus or minus 3 days)	No