REM Behavior DisorderNCT00745030
Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism
A study testing Rozerem in people with REM Behavior Disorder and Parkinsonism, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- REM Behavior Disorder, Parkinsonism
- What is being tested?
- Rozerem
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Dec 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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®)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the detailed description
See above.
- Conditions
- REM Behavior Disorder, Parkinsonism
- Being tested
- Rozerem, Placebo
- Keywords
- Parkinson's disease, Multiple Systems Atrophy, Lewy Body Dementia
- Medical subject headings
- REM Sleep Behavior Disorder, Parkinsonian Disorders, Parkinson Disease, Lewy Body Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RozeremDrug
Also called Ramelteon, TAK-375
Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks.
PlaceboDrug
Placebo 8 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Ramelteon (TAK-375) 8mg tablets Receives: Drug: Rozerem |
| 2 | Placebo comparator | Placebo 8 mg tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (1)
Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study
no participants were recruited
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2009
- Study completionDec 2009
Why it stopped: Low subject recruitment and enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for REM Behavior DisorderStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- Tanya Simuni, M.D., Principal investigator, Northwestern University, Department of NeurologyAleksandar Videnovic, M.D., Study director, Harvard Medical School, Associate Professor of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745030
- Sponsor's protocol ID
- 07-028R
- Status last verified
- Dec 2023
- First submitted
- 28 Aug 2008
- Last updated
- 9 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1016/j.ncl.2004.06.006. No abstract available.
PubMed 15501360Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone. 2004;6 Suppl 1A:S7-15. doi: 10.1016/s1098-3597(04)90013-0.
PubMed 15259535Gagnon 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.
PubMed 12196654Schenck 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.
PubMed 3820495Boeve 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.
PubMed 12847154Boeve 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.
PubMed 11481685Schenck 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.
PubMed 8614500Boeve 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.
PubMed 14592300Takeuchi 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.
PubMed 11422870Kunz 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.
PubMed 10348479Roth 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.
PubMed 16709464Borja 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.
PubMed 17157111Chaudhuri 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.
PubMed 12438461
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Tolerability of Ramelteon in Patients With REM Behavior Disorder and Parkinsonism: A Placebo Controlled, Double Blind, Randomized, Prospective Pilot Study
- ClinicalTrials.gov ID
- NCT00745030
- Acronym / sponsor ID
- 07-028R
- Conditions
- REM Behavior Disorder, Parkinsonism
- Keywords
- Parkinson's disease, Multiple Systems Atrophy, Lewy Body Dementia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low subject recruitment and enrollment.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Jun 2008
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 1 Sep 2008 (estimated)
- Results
- Posted 10 Nov 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: RozeremRamelteon (TAK-375) 8mg tablets |
| 2 | Placebo comparator | Drug: PlaceboPlacebo 8 mg tablets |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RozeremAlso: Ramelteon, TAK-375Subjects take 1 8mg tablet 30 minutes before bedtime everyday for 8 weeks. | Drug | 1 |
| PlaceboPlacebo 8 mg tablets | Drug | 2 |
Primary outcome
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
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.
1 secondary outcome
Change in the Amount of Tonic Muscle Activity Based on the Results of the Baseline and Final Polysomnographic (PSG) Study
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15501360Simuni 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.
- Background: PubMed 15259535Thorpy MJ. Sleep disorders in Parkinson's disease. Clin Cornerstone. 2004;6 Suppl 1A:S7-15. doi: 10.1016/s1098-3597(04)90013-0.
- Background: PubMed 12196654Gagnon 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.
- Background: PubMed 3820495Schenck 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.
- Background: PubMed 12847154Boeve 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.
- Background: PubMed 11481685Boeve 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.
- Background: PubMed 8614500Schenck 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.
- Background: PubMed 14592300Boeve 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.
- Background: PubMed 11422870Takeuchi 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.
- Background: PubMed 10348479Kunz 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.
- Background: PubMed 16709464Roth 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.
- Background: PubMed 17157111Borja 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanya Simuni, M.D. principal investigator
Northwestern University, Department of Neurology
Aleksandar Videnovic, M.D. study director
Harvard Medical School, Associate Professor of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rozerem in people with REM Behavior Disorder and Parkinsonism, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00745030, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.