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Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism
This study has been terminated.
( Low subject recruitment and enrollment. )

First Received on August 28, 2008.   Last Updated on April 18, 2011   History of Changes
Sponsor: Northwestern University
Collaborator: Takeda Global Research & Development Center, Inc.
Information provided by: Northwestern University
ClinicalTrials.gov Identifier: NCT00745030
  Purpose

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 Intervention
REM Behavior Disorder
Parkinsonism
 Drug: Rozerem
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Perry syndrome
MedlinePlus related topics: Parkinson's Disease Sleep Disorders
Drug Information available for: Ramelteon
U.S. FDA Resources

Further study details as provided by Northwestern University:

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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
  • Changes in Mean TST, LPS, WASO (Based on PSG) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Changes in Clinician Global Impression Scale of Improvement (CGI-I) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Changes in RBD Structured Questionnaire (Completed by Patient and Bed Partner) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Patient Completed Parkinson's Disease Sleep Scale (PDSS)- the Only Validated PD Specific, Questionnaire-based, Sleep Evaluation Scale [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Patient Completed Epworth Sleepiness Scale (ESS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Beck Depression Inventory (BDI) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Pittsburgh Sleep Quality Index (PSQI) (Patient Completed) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Patient Completed The Fatigue Severity Scale (FSS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Patient Completed PDQ-39 Scale(PD-specific Quality of Life Scale) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Physician Completed United Parkinson's Disease Rating Scale (UPDRS) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in Mini-Mental State Exam (MMSE) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Changes in The Montreal Cognitive Assessment Scale (MoCA) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Study Terminated Due to Low Subject Recruitment and Enrollment. [ Designated as safety issue: No ]
    Low subject recruitment and enrollment


Enrollment: 3
Study Start Date: June 2008
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Rozerem
Placebo Comparator: 2
Placebo 8 mg tablets
 Drug: Placebo
Placebo 8 mg tablets

Detailed Description:

See above.

  Eligibility

Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00745030

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Takeda Global Research & Development Center, Inc.
Investigators
Principal Investigator: Tanya Simuni, M.D. Northwestern University, Department of Neurology
Study Director: Aleksandar Videnovic, M.D. Northwestern University, Department of Neurology
  More Information

Additional Information:
Northwestern University Parkinson's Disease Center Clinical Trials Website  This link exits the ClinicalTrials.gov site

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. No abstract available.
Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone 2004; 6 Suppl 1A:S7-15.
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.

Responsible Party: Tanya Simuni, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT00745030     History of Changes
Other Study ID Numbers: 07-028R
Study First Received: August 28, 2008
Results First Received: October 12, 2010
Last Updated: April 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Parkinson's disease
Multiple Systems Atrophy
Lewy Body Dementia

Additional relevant MeSH terms:
Mental Disorders
Parkinsonian Disorders
REM Sleep Behavior Disorder
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Movement Disorders
REM Sleep Parasomnias
Parasomnias
Sleep Disorders

ClinicalTrials.gov processed this record on May 24, 2012



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