Open Label, Pilot Study of Adjunctive Xyrem (Sodium Oxybate) for the Treatment of Schizophrenia and Associated Sleep Disturbances
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Pittsburgh Sleep Quality Index
研究概览
简要总结
The present protocol proposes study of the recently approved compound sodium oxybate (Xyrem), a gamma-aminobutyric acid type b (GABAB) and a g-hydroxybutyric acid (GHB) receptor agonist, for the study of persistent symptoms of schizophrenia. Sodium oxybate is a central nervous system depressant currently approved for treatment of narcolepsy associated with cataplexy and excessive daytime sleepiness. In addition to evaluating effects on sodium oxybate on persistent symptoms and neurocognitive deficits in schizophrenia, the study will test the hypothesis that this medication may be particularly effective in combating Insomnia Related to Schizophrenia, and in normalizing symptomatic and polysomnographic manifestations of sleep-related brain dysfunction in schizophrenia.
详细描述
Rationale/Study Hypothesis:
Rationale for study of sodium oxybate is twofold: first, sleep dysfunction is an important and overlooked aspect of schizophrenia intrinsically linked to cognitive and functional impairments, and, second, GABAB receptors regulate dopaminergic and glutamatergic systems in vivo, suggesting that GABAB agonists may be therapeutically beneficial in schizophrenia.
We are aware of three previous trials of GHB in schizophrenia, two of which did not show any overall benefit in psychopathology. We noted multiple limitations in the controlled trials, including:
- requirement of cumbersome dosing patterns (up to six times a day) that could have led to incomplete compliance,
- lack of objective measures of subjective sleep or sleep architecture,
- lack of objective cognitive testing,
- use of GHB as monotherapy or only in conjunction with only low dose antipsychotics,
- short trial duration (less than 4 weeks),
- relatively low overall night-time dose of GHB, and
- a heterogeneous, small sample.
We propose an open label, proof of concept study evaluating the effect of sodium oxybate on insomnia in schizophrenia. The primary hypothesis of the study is that patients treated with sodium oxybate will show improved subjective sleep as measured by the overall Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index. Secondarily, we expect superior reduction in total psychopathology and PANSS factor scales (PANSS), polysomnographic measures, and neurocognition (MATRICS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-45 with a DSM-IV diagnosis of schizophrenia and insomnia related to schizophrenia, confirmed by a structured interview (SCID).
排除标准
- •Lack of capacity to give informed consent (capacity is determined by a licensed member of the treatment team).
- •Unstable medical illness.
- •Diagnosis of restless leg syndrome, a seizure disorder, uncontrolled hypertension, unstable cardiac illness, or obstructive sleep apnea.
- •Pregnancy or lack of adequate birth control.
- •History of substance dependence disorder.
- •Current treatment with valproic acid.
- •Succinic semialdehyde dehydrogenase deficiency (SSADH).
- •Persistent need for treatment with benzodiazepines, barbiturates, opiates or other sedative hypnotics.
研究组 & 干预措施
Sodium oxybate
Active treatment
干预措施: Sodium Oxybate (Drug)
结局指标
主要结局
Pittsburgh Sleep Quality Index
时间窗: 1 month
This rating scale generates a global sleep-quality score, as well as scores on 7 components of sleep quality: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The 19 items are combined to form seven "component" scores, each of which has a range of O-3 points. The seven component scores are then added to yield one "global" score, with a range of O-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas.
Epworth Sleepiness Scale
时间窗: 1 month
Designed to measure daytime sleepiness. 8 items rated 0-3, with higher scores associated with a greater daytime sleepiness. overall score rated 0-24, with scores greater than 10 indicating significant daytime sleepiness.
次要结局
- Positive and Negative Syndrome Scale (PANSS) Negative Factor(1 month)
- MATRICS Neurocognitive Battery Composite(1 month)
- Slow Wave Sleep Minutes(1 month)
研究者
Daniel C. Javitt, MD, PhD
Director, Schizophrenia Research Center
Nathan Kline Institute for Psychiatric Research