Parkinsonism, REM Behavior Disorder
Conditions
Keywords
Parkinson's disease, Multiple Systems Atrophy, Lewy Body Dementia
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.
Interventions
DRUGRozerem
Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks.
DRUGPlacebo
Placebo 8 mg tablets
Sponsors
Northwestern University
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study | 8 weeks | no participants were recruited |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ramelteon (TAK-375) 8mg Tablets Ramelteon (TAK-375) 8mg tablets | 1 |
| Placebo 8 mg Tablets Placebo 8 mg tablets | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Placebo 8 mg Tablets | Ramelteon (TAK-375) 8mg Tablets | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Continuous | 57 years STANDARD_DEVIATION 7.85 | 57 years STANDARD_DEVIATION 0 | 57 years STANDARD_DEVIATION 7.85 |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
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
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.
Time frame: 12 weeks
Population: We had difficulties with recruitment and did not manage to recruit enough participants so no data was collected and the study was terminated.
Secondary
Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study
no participants were recruited
Time frame: 8 weeks
Population: We had difficulties with recruitment and did not manage to recruit enough participants so no data was collected and the study was terminated.