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

20 Years
90 Years
Not Enrolling
Huntington's Disease, Parkinson's Disease, Dementia With Lewy Bodies, Sleep Disorders, Circadian Dysregulation

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Trial Information

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

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.

Inclusion 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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Sleep efficiency and other actigraphy derived sleep parameters

Outcome Time Frame:

2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention

Safety Issue:


Principal Investigator

Kaloyan S Tanev, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Institutional Review Board

Study ID:




Start Date:

May 2009

Completion Date:

July 2010

Related Keywords:

  • Huntington's Disease
  • Parkinson's Disease
  • Dementia With Lewy Bodies
  • Sleep Disorders
  • Circadian Dysregulation
  • Huntington's chorea
  • Huntington's Disease
  • Parkinson's Disease
  • Parkinsonism
  • Dementia
  • Dementia with Lewy Bodies
  • Actigraphy
  • Circadian dysregulation
  • Sleep Disorders
  • Circadian rhythm
  • Basal Ganglia Diseases
  • Dementia
  • Ganglion Cysts
  • Huntington Disease
  • Parkinson Disease
  • Sleep Disorders
  • Parasomnias
  • Neurodegenerative Diseases
  • Lewy Body Disease
  • Chronobiology Disorders



Massachusetts General Hospital Boston, Massachusetts  02114-2617