Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00745030

Recruitment Status : Terminated (Low subject recruitment and enrollment.)

First Posted : September 1, 2008

Results First Posted : November 10, 2010

Last Update Posted : April 21, 2011

Sponsor:

Collaborator:

Takeda

Information provided by:

Northwestern University

Study Description

Brief Summary:

Parkinson's disease (PD) is the second most common neurodegenerative disorder of the elderly that affects a million patients in US. Sleep dysfunction impacts up to 90% of PD patients. PD patients experience a variety of sleep disorders including parasomnias, specifically REM behavior disorder (RBD) that can precede the onset of motor manifestations of PD. RBD has negative consequences on patients' and their bed partners' quality of life mainly due to its impact on the sleep quality and day time alertness. RBD also predisposes affected individuals and their bed partners to physical injuries.

There are no FDA approved treatments for RBD. Clonazepam is the most commonly used treatment but carries risks of daytime sedation, tolerance, and withdrawal symptoms. More recently, melatonin has been demonstrated to be effective in several small studies. Ramelteon, a selective melatonin receptor agonist with favorable safety profile, could potentially be effective for the treatment of RBD.

This pilot protocol will investigate safety and efficacy of ramelteon for the treatment of RBD in subjects with parkinsonism. We plan to recruit 20 subjects with RBD diagnosed based on the clinical interview and confirmed by the polysomnographic (PSG) data. The study is designed as a prospective randomized placebo controlled 12-week study. Primary outcome measure will be change in frequency of RBD events based on the daily sleep diaries. Secondary outcome measure will be change in the amount of tonic muscle activity based on the results of the baseline and final PSG. A number of other secondary and exploratory outcome measures will be collected

Condition or disease	Intervention/treatment	Phase
REM Behavior Disorder Parkinsonism	Drug: Rozerem Drug: Placebo	Not Applicable

Detailed Description:

See above.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Efficacy and Tolerability of Ramelteon in Patients With REM Behavior Disorder and Parkinsonism: A Placebo Controlled, Double Blind, Randomized, Prospective Pilot Study
Study Start Date :	June 2008
Actual Primary Completion Date :	December 2009
Actual Study Completion Date :	December 2009

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Perry syndrome Dementia with Lewy bodies

Drug Information available for: Ramelteon

Genetic and Rare Diseases Information Center resources: Multiple System Atrophy

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 Ramelteon (TAK-375) 8mg tablets	Drug: Rozerem Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks. Other Names: Ramelteon TAK-375
Placebo Comparator: 2 Placebo 8 mg tablets	Drug: Placebo Placebo 8 mg tablets

Outcome Measures

Primary Outcome Measures :

Change in the Frequency of RBD Based on the Daily Sleep Diaries, Completed Daily for the Duration of the Study by the Study Subjects' Bed Partners/Caregivers [ Time Frame: 12 weeks ]
Change in the frequency of RBD based on the daily sleep diaries, completed daily for the duration of the study by the study subjects' bed partners/caregivers.

Data will not be analyzed. The protocol is being terminated due to low subject enrollment and recruitment.

Secondary Outcome Measures :

Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study [ Time Frame: 8 weeks ]
Changes in Mean TST, LPS, WASO (Based on PSG) [ Time Frame: 8 weeks ]
Changes in Clinician Global Impression Scale of Improvement (CGI-I) [ Time Frame: 10 weeks ]
Changes in RBD Structured Questionnaire (Completed by Patient and Bed Partner) [ Time Frame: 12 weeks ]
Changes in Patient Completed Parkinson's Disease Sleep Scale (PDSS)- the Only Validated PD Specific, Questionnaire-based, Sleep Evaluation Scale [ Time Frame: 12 weeks ]
Changes in Patient Completed Epworth Sleepiness Scale (ESS) [ Time Frame: 12 weeks ]
Changes in Beck Depression Inventory (BDI) [ Time Frame: 12 weeks ]
Changes in Pittsburgh Sleep Quality Index (PSQI) (Patient Completed) [ Time Frame: 12 weeks ]
Changes in Patient Completed The Fatigue Severity Scale (FSS) [ Time Frame: 12 weeks ]
Changes in Patient Completed PDQ-39 Scale(PD-specific Quality of Life Scale) [ Time Frame: 12 weeks ]
Changes in Physician Completed United Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: 12 weeks ]
Changes in Mini-Mental State Exam (MMSE) [ Time Frame: 12 weeks ]
Changes in The Montreal Cognitive Assessment Scale (MoCA) [ Time Frame: 12 weeks ]
Study Terminated Due to Low Subject Recruitment and Enrollment.
Low subject recruitment and enrollment

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of parkinsonism (idiopathic PD, multiple systems atrophy, Lewy body dementia)
RBD frequency of at least once per week based on the RBD screening clinical questionnaire
PSG evidence of RBD
Presence of bed partner/caregiver who sleeps in the same room as PD patient

Exclusion Criteria:

Known hypersensitivity to ramelteon or related compounds, including melatonin and melatonin-related compounds.
Use of hypnotics or other sedatives within a month prior to the study initiation
Presence of active psychosis
Use of neuroleptics, except for the atypical neuroleptics - specifically quetiapine (the dose should not exceed 50mg/day)
Use of antidepressants unless the patient has been on a stable dose for at least three months
Use of Venlafaxine (Effexor®)
Presence of cognitive impairment, defined as the Mini Mental Status Examination (MMSE) score <24
Presence of depression defined as the Beck Depression Inventory (BDI) score >14
Significant sleep disordered breathing (defined as an apnea-hypopnea index>15 events/hr of sleep on screening PSG), significant periodic limb movement disorder (defined as a PLM index>10 events/hr of sleep with awakening on screening PSG)
Travel through two time zones within a month prior to the study initiation

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00745030

Locations

Layout table for location information

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Takeda

Investigators

Layout table for investigator information

Principal Investigator:	Tanya Simuni, M.D.	Northwestern University, Department of Neurology
Study Director:	Aleksandar Videnovic, M.D.	Northwestern University, Department of Neurology

More Information

Publications:

Simuni T. Somnolence and other sleep disorders in Parkinson's disease: the challenge for the practicing neurologist. Neurol Clin. 2004 Oct;22(3 Suppl):S107-26. Review.

Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone. 2004;6 Suppl 1A:S7-15. Review.

Gagnon JF, Bédard MA, Fantini ML, Petit D, Panisset M, Rompré S, Carrier J, Montplaisir J. REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease. Neurology. 2002 Aug 27;59(4):585-9.

Schenck CH, Bundlie SR, Patterson AL, Mahowald MW. Rapid eye movement sleep behavior disorder. A treatable parasomnia affecting older adults. JAMA. 1987 Apr 3;257(13):1786-9.

Boeve BF, Silber MH, Parisi JE, Dickson DW, Ferman TJ, Benarroch EE, Schmeichel AM, Smith GE, Petersen RC, Ahlskog JE, Matsumoto JY, Knopman DS, Schenck CH, Mahowald MW. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology. 2003 Jul 8;61(1):40-5.

Boeve BF, Silber MH, Ferman TJ, Lucas JA, Parisi JE. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov Disord. 2001 Jul;16(4):622-30.

Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996 Feb;46(2):388-93. Erratum in: Neurology 1996 Jun;46(6):1787.

Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003 Jul;4(4):281-4.

Takeuchi N, Uchimura N, Hashizume Y, Mukai M, Etoh Y, Yamamoto K, Kotorii T, Ohshima H, Ohshima M, Maeda H. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001 Jun;55(3):267-9.

Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999 May;14(3):507-11.

Roth T, Seiden D, Sainati S, Wang-Weigand S, Zhang J, Zee P. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med. 2006 Jun;7(4):312-8. Epub 2006 May 18.

Borja NL, Daniel KL. Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. Review.

Chaudhuri KR, Pal S, DiMarco A, Whately-Smith C, Bridgman K, Mathew R, Pezzela FR, Forbes A, Högl B, Trenkwalder C. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):629-35.

Layout table for additonal information

Responsible Party:	Tanya Simuni, MD, Northwestern University
ClinicalTrials.gov Identifier:	NCT00745030
Other Study ID Numbers:	07-028R
First Posted:	September 1, 2008 Key Record Dates
Results First Posted:	November 10, 2010
Last Update Posted:	April 21, 2011
Last Verified:	April 2011

Keywords provided by Northwestern University:


Parkinson's disease Multiple Systems Atrophy Lewy Body Dementia

Additional relevant MeSH terms:

Layout table for MeSH terms

Parkinsonian Disorders REM Sleep Behavior Disorder Mental Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases	Nervous System Diseases Movement Disorders REM Sleep Parasomnias Parasomnias Sleep Wake Disorders

To Top