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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Sleep efficiency and other actigraphy derived sleep parameters
2 weeks pre intervention; 4 weeks of the intervention; 2 weeks after intervention
Kaloyan S Tanev, MD
Massachusetts General Hospital
United States: Institutional Review Board
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|