Effects of Rasagiline on Sleep Disturbances in Parkinson's Disease (RaSPar)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effects of Rasagiline on Sleep Disturbances in PD: A Single Center, Randomized, Double-blind, Placebo run-in, Polysomnographic Clinical Phase IV Trial|
- Change in sleep efficacy [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]Change from baseline in sleep efficacy (% in time in bed (TIB) / sleep partial time (SPT)) in polysomnography at 8 weeks
- Change in PDSS-2 [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]Change from baseline in sleep quality at 8 weeks
- Change in other sleep parameters [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]Change from baseline in sleep parameters e.g. portion of REM-sleep (%), portion of slow wave sleep (%), portion of light sleep (%), sleep latency (min), REM-sleep latency (min) in polysomnography at 8 weeks
- Electrocardiography [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: Yes ]Number of participants with adverse events
- Laboratory parameter [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: Yes ]Number of participants with adverse events
|Study Start Date:||October 2011|
|Study Completion Date:||September 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Effect of Rasagiline on sleep parameters in PD Patients
Rasagiline tablets 1mg once daily for 8 weeks
Other Name: Azilect
Placebo Comparator: Placebo
Effect of placebo on sleep parameters in PD Patients
Placebo 1tablet once daily for 8 weeks
Sleeping disorders are very common in patients with Parkinson's Disease (PD). Mainly initiation and maintenance of sleep is disturbed, therefore many patients suffer from daytime sleepiness and sleep attacks. Polysomnographic studies showed increased sleep fragmentation and frequent awakenings, increased amount of wakefulness during time in bed as well as reduced sleep efficacy and deep sleep time. In addition, increased sleep latency, REM-latency and decreased amounts of REM sleep were documented.
PD patients also suffer from primary sleep disorders like sleep disordered breathing and especially REM sleep behaviour disorder (RBD)and periodic limb movements in sleep (PLMS).
Not only neurochemical changes affecting cholinergic and monoaminergic systems, nocturnal hypokinesia and rigidity and painful dystonia due to the disease itself, but also medication side effects lead to impaired sleep-wake-control and reduced REM sleep.
Although levodopa medication and dopamine agonists reduce nocturnal hypokinesia and therefore improve insomnia they also have a potential impact on daytime sleepiness and are able to cause sleep disruption. The impact of dopaminergic therapy is complex showing biphasic effects with increased wakefulness and decreased REM-sleep frequency via stimulation of dopamine D1 receptors whereas low doses promote sleep via dopamine D2 receptors. In addition, acting of dopamine agonists via dopamine D3 receptors might be responsible for daytime sleepiness and sleep attacks.
However, as stimulation of the subthalamic nucleus improves mainly motor skills but also shows an important increase in sleep duration and quality, it could be suggested that by decreasing nocturnal hypokinesia improvement in sleep quality can be achieved.
Rasagiline mesylate was developed as a selective and irreversible MAO-B- inhibitor which is - unlike Selegiline - not metabolized to amphetamine derivates which are found to be partly responsible for negative effects on RBD and REM-sleep as well as sleep efficacy. Rasagiline is able to delay the need for initiating dopaminergic therapy, improves motor function in early and moderate to advanced PD and was shown to exhibit neuroprotective potential.
As different mechanisms of dopaminergic medication on different dopamine receptors are still not fully elucidated and in contrast to selegiline no side effects due to development of amphetamine derivates need to be taken into consideration, this study is to aim at evaluating the effects on sleep and daytime sleepiness of treatment with Rasagiline mesylate.
As Rasagiline is able to improve motor skills it might have positive effects on sleep disruption by reducing nocturnal akinesia. As it was reported to cause less sleep disruption in PD Patients than placebo it might be able to improve sleep architecture. Until now no clinical trial using polysomnographic techniques was performed to evaluate the effects of Rasagiline on sleep.
To study the effects of Rasagiline on sleep disturbances measured by polysomnographic (PSG) evaluation of sleep efficacy and PDSS-2.
Secondary measures are other sleep variables measured by PSG. In addition, sleep quality and daytime sleepiness assessed by standardized scales as well as cognitive function, depression indices and QoL index are measured.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01442610
|Dresden University of Technology, Dept. of Neurology|
|Dresden, Germany, 01307|
|Principal Investigator:||Alexander Storch, MD||Dresden University of Technology, Dept. of Neurology|