Melatonin and Sleep in Patients With Epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Sleep Latency Wakefulness After Sleep Onset (WASO)
研究概览
简要总结
The prevalence of epilepsy is 1% in the USA. About 30% of epilepsy patients eventually become refractory to medical treatment. Co morbid conditions are becoming as important as seizure control as these affect overall wellbeing. Sleep related complaints are frequent in them including, frequent arousals, difficulty falling asleep and excessive daytime sleepiness. Polysomnography shows increased arousal index, sleep onset latency, and stage shifts and fragmented REM sleep. Poor sleep efficiency causes daytime fatigue, poor cognition and behavior and can worsen seizure control. Stabilizing sleep may improve seizure control. Melatonin is a naturally occurring hormone in the body involved in the regulation of circadian rhythm and exogenously given, has been shown to decrease sleep onset latency, arousals, and there-by increase sleep efficiency in healthy pediatric patients. Similar data does not exist in the patients with epilepsy. As sleep has important impact on epilepsy and overall functioning, it is important to study effect of melatonin in children with epilepsy.
We propose a randomized double blind placebo controlled trial with a cross-over design. Our hypothesis is that, for patients with epilepsy, administration of melatonin 30 minutes before bedtime for four weeks may:
- Improve the quality of sleep;
- Improve daytime functioning in terms of cognition, behavior and quality of life;
- Decrease epileptic potential. We will use polysomnography, electroencephalogram, psychomotor vigilance task, seizure diary, and questionnaires to assess the effect of melatonin on these domains. This study may help to improve the care of children with epilepsy.
详细描述
Hypothesis 1: Melatonin treatment improves the quality of sleep in patients with epilepsy.
Various studies evaluating sleep problems in patients with epilepsy using questionnaires have shown that 34-45% patients have sleep related problems [1-3]. Cortesi et al reported that children with seizures had higher sleep difficulties than their siblings and controls[4]. Bedtime difficulties, sleep fragmentation, daytime sleepiness, snoring and parasomnia were reported as sleep problems in this population [2, 4]. Patients with refractory seizures and using multiple antiepileptic drugs(AED) showed worse problems[5]. On polysomnography (PSG) these patients show increased arousal index, increased sleep onset latency, fragmented or reduced REM sleep, increased stage shifts and increased Stage 1 sleep and decreased stage 2 and slow wave sleep. [6-9] Melatonin has been shown to decrease sleep onset latency and increase total sleep time and subjectively improve sleep in healthy individuals.[10-15]. Various studies using fast release and sustained release formulations have suggested improvement in sleep efficiency and decreased arousals as well.[16-18] In a randomized placebo controlled study by Gupta et al[19], Melatonin was shown to subjectively improve sleep in patients with epilepsy. Studies in children with neurodevelopmental delay and autism along with epilepsy have also reported similar findings.[17, 20-23] Rationale: There are significant sleep disturbances in children with epilepsy. Melatonin has been shown to improve sleep in this group of patients. However, all these studies report improvement based on parent report and only one study is placebo-controlled. Our study will assess this in randomized placebo controlled fashion and will provide both subjective and objective improvement in sleep with the primary outcome being improved sleep efficiency on PSG.
Hypothesis 2: Melatonin improves daytime functioning in terms of cognition, behavior and quality of life in the patients with epilepsy.
Poor sleep and epilepsy both have detrimental effect on cognition.[24-27] Melatonin by improving sleep may improve cognitive functioning in these patients.
Some patients with epilepsy have poor behavior and psychiatric function.[28-30] Severity of these problems are related to the worsening of the sleep problems.[2, 4] Melatonin by improving sleep may improve the behavior in these patients.
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
- 6 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6-11 years (prepubertal based on tanner staging)
- •Patients with epilepsy (diagnosis based on ILAE).
- •Normal intelligence based on school placement (defined as age appropriate; an IEP due to epilepsy related causes is acceptable as is placement in a higher grade) or IQ>70 (testing done with in 12 months of enrollment)
- •No history of significant snoring- loud snoring every night outside of a room with closed door
- •Combined score of 30 or more on sleep fragmentation, parasomnia and daytime drowsiness subscales on SBQ.
排除标准
- •History of significant snoring- loud snoring every night heard outside of a room with closed door
- •Diagnosis of obstructive sleep apnea (OSA) or periodic limb movement disorder on PSG
- •Vagus nerve stimulator implanted
- •History of a major psychiatric disease (e.g. psychosis, major depression)
- •History of autism or pervasive development disorder
- •Severe neuro-developmental disabilities, as determined by PI
- •Clinically significant systemic organic disease, as determined by PI
- •Current use of melatonin or sustained release melatonin
- •Prior use of sustained release melatonin
- •Current use of any hypnotic medications except for medications used as a rescue treatment for seizures
- •Use of psychoactive or stimulant medication for attention deficit disorders
- •Subjects with immune disorders, lympho-proliferative disorders, and those taking oral corticosteroids or other immuno-suppressants
- •Subject or parent/legal guardian might not be reasonably expected to be compliant with or to complete the study.
研究组 & 干预措施
Melatonin
Subjects will take sustained release melatonin 30 minutes prior to bedtime for four weeks
干预措施: Melatonin (Drug)
Placebos
Subjects will take a placebo 30 minutes before bedtime for four weeks
干预措施: Placebos (Drug)
结局指标
主要结局
Sleep Latency Wakefulness After Sleep Onset (WASO)
时间窗: 13 weeks
Sleep Latency Wakefulness After Sleep Onset (WASO). Calculated as the sum of wake time minutes from sleep onset to the final awakening.
次要结局
- Seizure Frequency(13 weeks)