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

This study has been withdrawn prior to enrollment.
(unable to recruit subjects for study.Collaborator stopped funding for study as of 3/31/2010)
Sponsor:
Information provided by (Responsible Party):
Kaloyan Tanev, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00907595
First received: May 20, 2009
Last updated: November 2, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention
Huntington's Disease
Parkinson's Disease
Dementia With Lewy Bodies
Sleep Disorders
Circadian Dysregulation
Drug: Ramelteon
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treating Sleep Wake Cycle Disturbances in Basal Ganglia Neurodegenerative Disorder Subjects With Ramelteon- A Double Blind, Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Sleep efficiency and other actigraphy derived sleep parameters [ Time Frame: 2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • UHDRS, UPDRS, cognitive measures, mood symptoms, aggression measures, functional ability. [ Time Frame: 2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: May 2009
Study Completion Date: July 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ramelteon
Subjects randomized to Ramelteon
Drug: Ramelteon
After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.
Other Name: Ramelteon
Placebo Comparator: Placebo
Subjects randomized to placebo
Drug: Placebo
After 2 weeks of baseline sleep study, subjects will be randomized to take either Ramelteon or Placebo for 4 weeks.
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   20 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

We will recruit 24 Huntington's disease, Parkinson's Disease, or Dementia with Lewy Bodies subjects. Assuming a dropout rate of 20%, we expect that 20 of the 24 subjects who initially enroll will complete the study.

Inclusion criteria will be the following:

  • 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 will be the following:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00907595

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02144
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Kaloyan S Tanev, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Kaloyan Tanev, MD, Neuropsychiatrist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00907595     History of Changes
Other Study ID Numbers: 06-043R
Study First Received: May 20, 2009
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Huntington's chorea
Huntington's Disease
Parkinson's Disease
Parkinsonism
Dementia
Dementia with Lewy Bodies
Actigraphy
Circadian dysregulation
Sleep Disorders
Circadian rhythm

Additional relevant MeSH terms:
Lewy Body Disease
Parkinson Disease
Dementia
Disease
Huntington Disease
Sleep Disorders
Parasomnias
Chronobiology Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Pathologic Processes
Chorea
Dyskinesias
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Cognition Disorders
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on September 30, 2014