Treatment of Insomnia in Patients With Parkinson's Disease: A Multi-site, Placebo-controlled Study of Eszopiclone
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- TST
研究概览
简要总结
Parkinson's disease (PD) is the second most common neurodegenerative disease in the US, affecting nearly 1 million Americans. Up to 82% of community dwelling individuals with PD complain of sleep disturbances, typically sleep fragmentation. Despite the high prevalence of sleep problems and their impact on the life of these individuals, there has been, until recently, little research focus on the problem. This will be a multi-site, double blind, placebo-controlled, two arm, parallel group, fixed-dose trial which will last 6 weeks. Seventy patients at four sites (30 at the PI's site and a total of 40 patients at three external sites) will be equally randomized to eszopiclone or placebo. The primary hypothesis is that eszopiclone will be superior to placebo for the treatment of insomnia in patients with Parkinson's disease
详细描述
Introduction and Rationale Parkinson's disease (PD) is the second most common neurodegenerative disease in the US, affecting nearly 1 million Americans. Up to 82% of community dwelling individuals with PD complain of sleep disturbances, typically sleep fragmentation. This difficulty with sleep maintenance is accompanied by a decrease in total sleep time and an increase in the number of awakenings and wakefulness after sleep. The interactions between PD and sleep are complicated and many PD patients with insomnia have concomitant sleep disorders such as REM Sleep Behavior Disorder (RBD), Periodic Limb Movements of Sleep (PLMS) and Sleep Disordered Breathing (SDB). Nonetheless, the majority of patients appear to have insomnia that is an integral symptom of PD rather than being related to specific sleep disorders. Sleep difficulties in patients with PD are independent and important predictors of poor quality of life. In addition, sleep disturbances contribute to excessive daytime sleepiness (EDS) and poor daytime functioning as well as patients' reduced enthusiasm for daily events and impairment in the quality of life of their spousal caregivers7. There are, therefore, a variety of reasons for us to address sleep problems in patients with PD.
Despite the high prevalence of sleep problems and their impact on the life of these individuals, there has been, until recently, little research focus on the problem. While researchers have now begun to describe the phenomenology and epidemiology of sleep in PD, there have few treatment studies from which the clinical community can derive guidance. Despite this lack of evidenced-based clinical guidance, community surveys indicate that up to 40% of patients with PD are taking sleeping pills.3 Data published in 1999 indicate that the two most commonly used hypnotics in general practice were trazodone and zolpidem. More recent data continue to show that trazodone is prescribed even more frequently than zolpidem. We have recently completed a survey of 50 Parkinson's disease experts and found that the most commonly used hypnotics were zolpidem and trazodone. Of note is also that these experts estimated that 40% of their patients with PD were using sleep medications.
We have then the following clinical problem in the treatment of patients with PD. Insomnia is very common and is strongly associated with a variety of adverse outcomes but there are no controlled data that can guide the approach to the treatment of these individuals. Nevertheless, clinicians appear to be using a number of hypnotics, principally zolpidem and trazodone, neither of which have been evaluated in PD or for long term use.
Objectives
To test the safety and efficacy of eszopiclone for the treatment of insomnia in patients with Parkinson's disease
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
- 35 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parkinson's disease by research criteria. Research criteria for PD include, (1) the presence of at least 2 of the following signs: resting tremor, cogwheel rigidity, bradykinesia, or postural reflex impairment, at least 1 of which must be either resting tremor or bradykinesia, (2) no other cause of parkinsonism, (3) no signs of more extensive neurodegeneration indicating atypical parkinsonism, and (4) a clear-cut response to levodopa or dopamine agonist.
- •Sleep maintenance insomnia (at least 3 of 7 nights of at least 2 awakenings nightly, or a total sleep time of < 6.5 hours) or sleep latency insomnia (at least 3 of 7 nights of sleep latency > 30 minutes), as well as clinically significant daytime distress or impairment during the 2 week self assessment prior to baseline.
- •Patients aged 35-85 years.
- •Patients must have completed at least the 9th grade and be fluent in English.
- •If a female of child bearing potential, the patient must be non-pregnant and either post-menopausal or using an approved birth control method. Patients must have a negative urine pregnancy test at the screen visit.
- •Antidepressants will be allowed if the patient has been on a stable dose for at least one month.
- •Benzodiazepines will be allowed if taken during the day prior to 6pm and it is not taken as a sleep aid.
- •Other medications with CNS activity that the patient is on at screening, e.g., dopaminergic drugs, B-blockers, etc, will be kept constant throughout the acute phase.
排除标准
- •Evidence on PSG and symptoms or complaints (as defined below) of, significant sleep disordered breathing (central or obstructive apnea), periodic limb movement disorder (PLMD), or REM sleep behavior disorder (RBD).
- •Significant sleep disordered breathing will be defined as an AHI > 15 events/hr of sleep and/or significant hypoxemia on screening PSG; significant PLMD will be defined as a PLM index > 25 events/hr of sleep on screening PSG; RBD will be defined based on presence of both clinical symptomatology (demonstrated injury to self or others during sleep) as well as PSG criteria (intermittent loss of REM atonia).
- •No significant dementia. Significant dementia is operationalized as a score of less than 26 on the Mini-Mental State Examination (MMSE).
- •Insomnia is not primarily due to serious depression or anxiety in the opinion of the investigator.
- •Any current (within three months) diagnosis of alcohol or substance abuse/dependence (with the exception of nicotine dependence).
- •Currently on psychotropic medications, other than antidepressants or benzodiazepines. If the patient is on other psychotropics, and can be safely removed from these medications at the time of initial screening, there will be a washout period prior to entering the study.
- •Sleep medication that the patient is on during screening will be tapered prior to randomization.
- •Any unstable medical disorder that would interfere with the study.
- •Patients with a known history of non-response or lack of toleration to adequate doses of zolpidem or trazodone.
- •Patients currently receiving CBT for insomnia.
- •Patients who are unable to be maintained on their current dose of PD medications throughout the trial.
研究组 & 干预措施
eszopiclone
eszopiclone. Those under 65yo received 3mg of eszoplicone ( or randomized to matching placebo)and those 65yo or older received 2mg of eszoplicone ( or randomized to matching placebo)taken each night at bedtime
干预措施: eszopiclone (Drug)
placebo
Those randomly assigned to matching placebo, took their dose each night at bedtime
干预措施: placebo (Other)
结局指标
主要结局
TST
时间窗: 6 weeks
Total sleep time in hours
次要结局
- WASO(6 weeks)