Official Title: “Efficacy and Tolerability of Ramelteon in Patients With REM Behavior Disorder and Parkinsonism: A Placebo Controlled, Double Blind, Randomized, Prospective Pilot Study”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2009

See above.

Intervention(s) in this Clinical Trial

• Drug: Rozerem
  • Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks.
• Drug: Placebo
  • Placebo 8 mg tablets

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Ramelteon (TAK-375) 8mg tablets
• Placebo Comparator: 2
  • Placebo 8 mg tablets

Primary 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
    Safety Issue?: No

Secondary 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
    Safety Issue?: No
• Changes in mean TST, LPS, WASO (based on PSG)
  • Time Frame: 8 weeks
    Safety Issue?: No
• Changes in Clinician global impression scale of improvement (CGI-I)
  • Time Frame: 10 weeks
    Safety Issue?: No
• Changes in RBD Structured Questionnaire (completed by patient and bed partner)
  • Time Frame: 12 weeks
    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
    Safety Issue?: No
• Changes in patient completed Epworth sleepiness scale (ESS)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in Beck Depression Inventory (BDI)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in Pittsburgh Sleep Quality Index (PSQI) (patient completed)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in patient completed The Fatigue Severity Scale (FSS)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in patient completed PDQ-39 scale(PD-specific quality of life scale)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in physician completed United Parkinson's Disease Rating Scale (UPDRS)
  • Time Frame: 12 weeks
    Safety Issue?: No
• Changes in Mini-Mental State Exam (MMSE)
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Changes in The Montreal Cognitive Assessment Scale (MoCA)
  • Time Frame: 12 weeks
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Northwestern University

Overall Clinical Trial Officials and Contacts

Tanya Simuni, M.D. Principal Investigator Northwestern University, Department of Neurology  

Overall Contact: Teresa A Kuhta, BS 312-503-1999 t-kuhta@northwestern.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00745030

Study ID Number: 07-028R

ClinicalTrials.gov Identifier: NCT00745030

Health Authority: United States: Food and Drug Administration

Northwestern University Parkinson's Disease Center Clinical Trials Website