Double Bind Randomized Placebo-controlled Cross-over Study to Evaluate Effect of Continuous Apomorphine During the Night on Sleep Disorders in Insomniac Patients With Parkinson's Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 9
- 主要终点
- Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence
研究概览
简要总结
The purpose of the study is to demonstrate that continuous apomorphine treatment during the night compared with placebo improves sleep quality in insomniac patient with Parkinson's disease.
详细描述
Sleep disorders are very common in Parkinson's disease (PD). They are present in almost all patients. They have an important impact on quality of life. To improve the comfort of patients, neurologists typically offer either dispersible form of levodopa, prolonged release dopaminergic agonists treatments or deep brain stimulation surgery. Unfortunately these treatments are too short-acting for the dispersible form of levodopa or not always sufficient for the oral or transdermal dopamine agonist or are very heavy to implement as surgery.
Some sleep disorders such as restless legs syndrome and periodic leg movements, and obstructive sleep apnoea syndrome, seem to be more frequent in PD patients than in general population and could be improved by a continuous dopaminergic treatment the night.
Finally, daytime sleepiness is a major problem in PD patients. Although it seems most often linked to dopaminergic treatments given during the day, it could also be, in some patients the result of a very bad night's sleep, leading to a rebound of sleep during the day.
The main objective is to demonstrate that compared with placebo, nocturnal continuous apomorphine treatment improves sleep quality assessed by the patient on the PDSS-2 scale in fluctuating parkinsonian patients with complaints of insomnia.
The secondary objectives are to measure the effectiveness of nocturnal continuous apomorphine on sleep quality : total sleep time, sleep efficiency, arousal index, ventilatory events and legs movements indexes, to measure the relative proportion of sleep stages (N1, N2, N3, Rapid Eye Movement ou REM sleep), position changes during sleep index and the percentage of time spent in the supine position, percentage of time with SpO2 <90%), sleepiness (Epworth and Multiple Sleep Latency Test) and their consequences on quality of life (EuroQol 5), depressive symptoms (Beck II), anxiety (STAI), overall cognition (MOCA), pain and engine condition after waking up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 35 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic Parkinson's disease ( Hughes AJ et al. 2001)
- •Patients with motor fluctuations
- •Chronic Insomnia disorder criteria according to the criteria of DMS- V ( American Psychiatric Association, 2013) and insomnia severity index > 15
- •Able to use independently the device required for treatment by apomorphine
- •Collection of written informed consent (legal obligation for any project under the public health law , bioethics laws and / or CNIL) .
- •Affiliate to social security or beneficiary of such a regime
排除标准
- •Atypical Parkinsonian Syndromes
- •Parkinson's disease with dementia (Montreal Cognitive Assessment (MoCA) <25/30 (NASREDDINE and al., 2012))
- •Parkinson's disease with hallucinations
- •Parkinson's disease with impulse Control disorder (ICD)
- •Parkinson's disease already treated with APOMORPHINE pump or justifying the use of the pump continuously day and night
- •Another obvious severe disease explaining insomnia
- •Exclusion for monitoring difficulties (mutation, insufficient motivation, priority associated pathology in care)
- •Patient unwilling to accept a pump
- •Patient not accepting polysomnography and multiple sleep latency test
- •Patient with health problems or a skin disease precluding continuous subcutaneous infusion
- •Female parturient or nursing
- •Cardiac dysrhythmia precluding treatment with domperidone or apomorphine (increased QTc ≥ 440 ms in men, QTc ≥ 450 ms in women)
- •Treatments forbidden in association with apomorphine such as:
- •antiemetic neuroleptics
- •Tetrabenazine
- •Excessive alcohol consumption
- •Contraindications for apomorphine:
- •Hypersensitivity to apomorphine or one of the excipients
- •Respiratory Depression
- •Hepatic impairment
- •Intellectual Disability
研究组 & 干预措施
Apomorphine (5 mg/ml)
Active phase is apomorphine (from 0.5 mg (0.1 ml) to maximum 5 mg (1 ml)/hour of apomorphine), delivered with a pump (subcutaneous administration), during 22 days.
干预措施: Apomorphine (Drug)
Physiologic serum
Physiological serum (from 0.1 ml to maximum 1 ml/ hour), delivered with a pump (subcutaneous administration), during 22 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline PDSS2 score (Parkinson's Disease Sleep Scale) at the end of the sequence
时间窗: 53 days
This score is a score range, it's the difference between PDSS2 score at day18 and day 1 (for the first sequence) and difference between day 53 and day 36 (for the second sequence).
次要结局
- Total sleep time period(53 days)
- Sleep efficiency (total sleep time based on the total sleep period)(53 days)
- Total sleep time (non-Rapid Eye Movements (REM) stages 1,2,3 plus REM sleep)(53 days)
- Length of the intra-sleep wakefulness(53 days)
- Duration of each sleep stage of the total sleep time(53 days)
- Arousal index(53 days)
- Apnea / hypopnea Index(53 days)
- Percentage of time spent with a saturation below 90%(53 days)
- Periodic leg movement index(53 days)
- Percentage of REM sleep time with tonic and phasic activity(53 days)
- Objective sleepiness on Multiple Sleep Latency Test(53 days)
- Subjective sleepiness on the Epworth Sleepiness Scale(53 days)
- Sleep latency (between light extinction and the first period of sleep)(53 days)