Treating Sleep/Wake Cycle Disturbances in Basal Ganglia Disorders With Ramelteon

NCT ID: NCT00907595

Last Updated: 2012-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2010-07-31

Brief Summary

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The proposed study is a double-blind, placebo controlled pilot study of HD, PD, and DLB subjects with sleep disturbances. This study is designed to determine the effects of 4 weeks Ramelteon treatment on the sleep patterns of people with basal ganglia disorders such as HD, PD and DLB. The study also aims to look at the sleep patterns of caregivers of people with HD, PD and DLB.

Detailed Description

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Huntington's disease (HD) is a progressively degenerative brain disorder, which results in a loss of mental and physical abilities. It is genetically determined and people carrying the HD gene invariably develop the clinical disorder at some point in their lives. HD symptoms consist of neuropsychiatric changes and motor movements. Once present, the symptoms are progressive in nature and eventually fatal. Currently there is no cure for HD.

Like HD, Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB) are also neurodegenerative disorders affecting the basal ganglia. PD and DLB are synucleinopathies - i.e., they are associated with dysfunction of the protein alpha-synuclein. Unlike HD, PD and DLB are not inherited in an autosomal dominant manner.

Sleep/wake cycles in HD, PD and DLB. HD patients, especially those in moderate to severe stages of the disease, frequently complain of difficulty falling and staying asleep. Little is known about the phenomenology and pathophysiology of sleep disturbances in HD. The few studies that have addressed this issue of sleep in HD have found disturbances in sleep architecture and sleep/wake cycles. Overall, the literature on sleep and other circadian disturbances in HD is very limited. If sleep/wake cycle disturbances in HD have pathophysiological mechanisms similar to other neurodegenerative disorders, then Ramelteon, a hypnotic agent and melatonin receptor agonist, may be beneficial in sleep/wake cycle disturbances in HD.

Sleep disruptions and circadian sleep disruptions are integral to the clinical presentation of both PD and DLB. As is true in HD, sleep disturbances in PD and DLB cause severe disruption to the patients and their caregivers' lives. In PD, sleep dysfunction occurs in approximately two thirds of patients. Sleep problems range from difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, REM sleep behavior disorder (RBD), to excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in PD. In DLB, REM sleep behavior disorder (RBD) occurs years to decades before the onset of dementia. Importantly, melatonin is one of the main treatments used for RBD. Therefore, a melatonin agonist such as Ramelteon is a natural choice for the treatment of circadian sleep disturbances in PD and DLB.

Activity monitors (actigraphs) have been used as an alternative to polysomnography (PSG). Actigraphs are small electronic motion sensors that detect movements in three axes and provide information about the subjects' activity levels over periods of days to weeks. Using validated algorithms to infer wakefulness and sleep, investigators can draw conclusions about the individuals' sleep/wake cycle patterns from their activity patterns.

Conditions

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Huntington's Disease Parkinson's Disease Dementia With Lewy Bodies Sleep Disorders Circadian Dysregulation

Keywords

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Huntington's chorea Huntington's Disease Parkinson's Disease Parkinsonism Dementia Dementia with Lewy Bodies Actigraphy Circadian dysregulation Sleep Disorders Circadian rhythm

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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Ramelteon

Subjects randomized to Ramelteon

Group Type ACTIVE_COMPARATOR

Ramelteon

Intervention Type DRUG

After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.

Placebo

Subjects randomized to placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.

Interventions

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Ramelteon

After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.

Intervention Type DRUG

Placebo

After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Subjects with HD will be between the ages of 20 and 65 years old;
* Subjects with PD or DLB will be between the ages of 40 and 90;
* Subjects will have subjective complaints of sleeping problems or their caregivers will complain of the subjects not sleeping well
* Subjects with all severity of HD, PD, and DLB symptoms will be accepted as long as they complain of sleep problems
* A diagnosis of HD, PD, or DLB. For HD patients, a positive HD gene status for everyone except the caregivers will have been obtained for clinical reasons and will be known at the time of enrollment into the study. PD patients will have a clinical diagnosis of PD. DLB patients will have a diagnosis of possible or probably DLB based on consensus criteria (outlined in McKeith et al., 2005).
* Subjects will be willing and able to participate in the informed consent process.

Exclusion Criteria

* Subjects who are unable to participate in the informed consent process
* Subjects with previously documented primary sleep disorders (unrelated to HD, PD, or DLB), including Obstructive Sleep Apnea Syndrome, Periodic Limb Movement Disorder of Sleep, or Narcolepsy.
* Subjects taking fluvoxamine, rifampin, ketoconazole , and fluconazole within 30 days of baseline
* Subjects with hepatic impairment
* Subjects who perform shift work or have any other circadian rhythm abnormality or disruption
* Subjects who are diagnosed with a Major Depressive Episode, current at the time of enrollment (subject may have a history of a Major Depressive Episode as long as it is in partial or full remission at the time of enrollment)
* Subjects who are diagnosed with a manic or hypomanic episode, current at the time of enrollment (subject may have a history of a manic or hypomanic episode as long as it is in full remission at the time of enrollment)
* Subjects who at the time of enrollment receive hypnotic agents or have been on hypnotic agents during the two weeks prior to enrollment
* Subjects who are pregnant at the time of enrollment or intend to become pregnant during the period of study participation
* Subjects who in the opinion of the research personnel would not be able to participate in the research protocol because of agitation, lack of transportation, or other reasons.
Minimum Eligible Age

20 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Kaloyan Tanev, MD

Neuropsychiatrist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kaloyan S Tanev, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Hurelbrink CB, Lewis SJ, Barker RA. The use of the Actiwatch-Neurologica system to objectively assess the involuntary movements and sleep-wake activity in patients with mild-moderate Huntington's disease. J Neurol. 2005 Jun;252(6):642-7. doi: 10.1007/s00415-005-0709-z. Epub 2005 Mar 7.

Reference Type BACKGROUND
PMID: 15742112 (View on PubMed)

Morton AJ, Wood NI, Hastings MH, Hurelbrink C, Barker RA, Maywood ES. Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. J Neurosci. 2005 Jan 5;25(1):157-63. doi: 10.1523/JNEUROSCI.3842-04.2005.

Reference Type BACKGROUND
PMID: 15634777 (View on PubMed)

Ancoli-Israel S, Clopton P, Klauber MR, Fell R, Mason W. Use of wrist activity for monitoring sleep/wake in demented nursing-home patients. Sleep. 1997 Jan;20(1):24-7. doi: 10.1093/sleep/20.1.24.

Reference Type BACKGROUND
PMID: 9130330 (View on PubMed)

Other Identifiers

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06-043R

Identifier Type: -

Identifier Source: org_study_id