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

November 2, 2012 updated by: Kaloyan Tanev, MD, Massachusetts General Hospital

Treating Sleep Wake Cycle Disturbances in Basal Ganglia Neurodegenerative Disorder Subjects With Ramelteon- A Double Blind, Placebo Controlled Trial

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02144
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Sleep efficiency and other actigraphy derived sleep parameters
Time Frame: 2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention
2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention

Secondary Outcome Measures

Outcome Measure
Time Frame
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
2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Kaloyan S Tanev, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

July 1, 2010

Study Registration Dates

First Submitted

May 20, 2009

First Submitted That Met QC Criteria

May 21, 2009

First Posted (Estimate)

May 22, 2009

Study Record Updates

Last Update Posted (Estimate)

November 6, 2012

Last Update Submitted That Met QC Criteria

November 2, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-043R

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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