Clinical trial NCT00745030: Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: REM Behavior Disorder
Parkinsonism
Keywords: Parkinson's disease
Multiple Systems Atrophy
Lewy Body Dementia
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2008-09-01
Enrollment: 3
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: See above.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University, Department of Neurology
name: Tanya Simuni, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard Medical School, Associate Professor of Neurology
name: Aleksandar Videnovic, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone. 2004;6 Suppl 1A:S7-15. doi: 10.1016/s1098-3597(04)90013-0.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.