Effects of Rasagiline on Sleep Disturbances in PD: A Single Center, Randomized, Double-blind, Placebo run-in, Polysomnographic Clinical Phase IV Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in sleep efficacy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female outpatients
- •Age from 50 to 85 years
- •Definite Parkinson's disease according to UK brain bank criteria
- •Hoehn & Yahr I-III
- •Relevant sleep disturbance (> 5 point in PSQI)
- •Patient must be able to complete questionaires
- •Stable antiparkinsonian medication for at least 4 weeks prior to screening
- •Antiparkinsonian medication should be stable 30 days prior to screening until 10 days after end of study
- •Written informed consent
排除标准
- •Overreaction/allergies to study drug or one of its components
- •Pregnancy and/or lactation period
- •Women with childbearing potential not practicing an acceptable method of contraception (Pearl-Index <1)
- •Non-permitted medication within two weeks prior to study inclusion and during study: Hypnotics, Amantadine, MAO inhibitors, SSRIs, SNRIs, tricyclic and tetracyclic antidepressants, all neuroleptics except clozapine and quetiapine
- •Non-permitted medication during study: CYP P450 1A2 inhibitors (a.e. Ciprofloxacin, Cimetidine, Clarithromycin, Erythromycin, systemic Estrogen, Fluvoxamine, Isoniazid, Ketoconazole, Levofloxacin, Norfloxacin, Mexiletine, Paroxetine, Propafenone, Zileuton, Disulfiram, Ginseng, grapefruit juice, Ephedrine).
- •Planned participation or participation in another clinical trial during the last 4 weeks prior to screening and during the whole trial period
- •Epilepsy or epileptic seizure in the history
- •Significant renal or hepatic impairment
- •Legal incapacity or limited legal capacity
- •Dementia or other psychiatric illness that prevent from giving informed consent.
- •Any clinically significant medical illnesses which interfere with capability to participate in study
- •History of sleep related breathing disorder or severe OSAS as characterized by PSG (> 30 AHI)
- •Severe Depression (BDI > 17)
- •Known history of cardiac arrhythmias, angina pectoris, narrow angle glaucoma, residual urine caused by benign prostatic hyperplasia, pheochromocytoma
- •Patients requiring elective surgery requiring general anaesthesia during study period
研究组 & 干预措施
Rasagiline
Effect of Rasagiline on sleep parameters in PD Patients
干预措施: Rasagiline (Drug)
Placebo
Effect of placebo on sleep parameters in PD Patients
干预措施: Placebo (Drug)
结局指标
主要结局
Change in sleep efficacy
时间窗: baseline and 8 weeks
Change from baseline in sleep efficacy (% in time in bed (TIB) / sleep partial time (SPT)) in polysomnography at 8 weeks
Change in PDSS-2
时间窗: Baseline and 8 weeks
Change from baseline in sleep quality at 8 weeks
次要结局
- Change in other sleep parameters(baseline and 8 weeks)
- Electrocardiography(baseline and 8 weeks)
- Laboratory parameter(baseline and 8 weeks)