Effects of Rasagiline on Sleep Disturbances in Parkinson's Disease
Condition: Sleep Disturbances; Parkinsons's Disease
MeSH terms: Parkinson Disease; Dyssomnias; Parasomnias
Study type: Interventional
Phase: Phase 4

Summary: 
      As the MAO-B inhibitor 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 only
      minor sleep disruption in PD Patients, it might be able to improve sleep architecture. The
      investigators thus 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, sleep quality and daytime sleepiness assessed by
      standardized scales as well as cognitive function, depression and QoL index.
    

Detailed description: 
      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.
    

Intervention name(s): Rasagiline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Rasagiline tablets 1mg once daily for 8 weeks; Placebo 1tablet once daily for 8 weeks
Other intervention name(s): Azilect
Intervention MeSH terms: Rasagiline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Rasagiline; Sleep disorder; Parkinson's disease; Sleep Disturbances in patients with parkinsons's disease