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

NCT ID: NCT00745030

Last Updated: 2024-01-09

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2009-12-31

Brief Summary

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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

Detailed Description

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See above.

Conditions

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REM Behavior Disorder Parkinsonism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Ramelteon (TAK-375) 8mg tablets

Group Type EXPERIMENTAL

Rozerem

Intervention Type DRUG

Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks.

2

Placebo 8 mg tablets

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo 8 mg tablets

Interventions

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Rozerem

Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks.

Intervention Type DRUG

Placebo

Placebo 8 mg tablets

Intervention Type DRUG

Other Intervention Names

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Ramelteon TAK-375

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takeda

INDUSTRY

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tanya Simuni, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northwestern University, Department of Neurology

Aleksandar Videnovic, M.D.

Role: STUDY_DIRECTOR

Harvard Medical School, Associate Professor of Neurology

Locations

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Northwestern University

Chicago, Illinois, United States

Site Status

Countries

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United States

References

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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. doi: 10.1016/j.ncl.2004.06.006. No abstract available.

Reference Type BACKGROUND
PMID: 15501360 (View on PubMed)

Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone. 2004;6 Suppl 1A:S7-15. doi: 10.1016/s1098-3597(04)90013-0.

Reference Type BACKGROUND
PMID: 15259535 (View on PubMed)

Gagnon JF, Bedard MA, Fantini ML, Petit D, Panisset M, Rompre 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. doi: 10.1212/wnl.59.4.585.

Reference Type BACKGROUND
PMID: 12196654 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3820495 (View on PubMed)

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. doi: 10.1212/01.wnl.0000073619.94467.b0.

Reference Type BACKGROUND
PMID: 12847154 (View on PubMed)

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. doi: 10.1002/mds.1120.

Reference Type BACKGROUND
PMID: 11481685 (View on PubMed)

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. doi: 10.1212/wnl.46.2.388.

Reference Type BACKGROUND
PMID: 8614500 (View on PubMed)

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. doi: 10.1016/s1389-9457(03)00072-8.

Reference Type BACKGROUND
PMID: 14592300 (View on PubMed)

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. doi: 10.1046/j.1440-1819.2001.00854.x.

Reference Type BACKGROUND
PMID: 11422870 (View on PubMed)

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. doi: 10.1002/1531-8257(199905)14:33.0.co;2-8.

Reference Type BACKGROUND
PMID: 10348479 (View on PubMed)

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. doi: 10.1016/j.sleep.2006.01.003. Epub 2006 May 18.

Reference Type BACKGROUND
PMID: 16709464 (View on PubMed)

Borja NL, Daniel KL. Ramelteon for the treatment of insomnia. Clin Ther. 2006 Oct;28(10):1540-55. doi: 10.1016/j.clinthera.2006.10.016.

Reference Type BACKGROUND
PMID: 17157111 (View on PubMed)

Chaudhuri KR, Pal S, DiMarco A, Whately-Smith C, Bridgman K, Mathew R, Pezzela FR, Forbes A, Hogl 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. doi: 10.1136/jnnp.73.6.629.

Reference Type BACKGROUND
PMID: 12438461 (View on PubMed)

Other Identifiers

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07-028R

Identifier Type: -

Identifier Source: org_study_id

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