Double-Blind, Randomized, Placebo-Controlled, Cross-Over Study of Intranasal Oxytocin Augmentation of Antipsychotic Medication in Schizophrenia Patients
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Total Score in the Positive and Negative Syndrome Scale (PANSS)
研究概览
简要总结
The objective of the study is to compare the efficacy of intranasal oxytocin versus intranasal placebo to improve symptoms in schizophrenia patients who have residual symptoms despite being on adequate treatment with antipsychotic medication.
详细描述
Schizophrenia patients treated with even the best currently available antipsychotic drugs continue to experience significant symptoms. There is a strong need for better treatments including treatments that can safely be given as adjunct to current antipsychotics in order to improve overall efficacy of treatment.
Oxytocin is a neurohypophyseal peptide best known for its role as a neurohormone involved in parturition and lactation. In addition to these well established peripheral effects, there is a compelling body of converging evidence indicating that oxytocin plays a critical role in the regulation of a number of diverse centrally-mediated behavioral and cognitive processes that are highly relevant to Schizophrenia, including social attachment and memory , (see Argiolas and Gessa 1990; McCarthy and Aaltemus 1997).Furthermore, several lines of research suggest that oxytocin receptors may be an important target for development of novel treatments for schizophrenia. Oxytocin and its receptors exist in several areas of the brain which have been heavily implicated in the pathophysiology of schizophrenia, such as the nucleus accumbens and the hippocampus, (Van Leeuwan et al 1985). Oxytocin administered peripherally inhibits dopamine transmission in the mesolimbic pathway (Sarnyai 1992) et al, 1990). Antipsychotics have been found to elevate the secretion of oxytocin in rats (Uvnas-Moberg et al 1992a) suggesting that endogenous oxytocin may play a role in the therapeutic effects of antipsychotic drugs.
Each subject will be enrolled for 6 week treatment period after a screening phase Study procedure involves weekly clinic visits as an outpatient. Forty patients will be randomly assigned to either 40 IU oxytocin twice daily or vehicle placebo. After 3 weeks, treatments will be crossed over such that subjects that received oxytocin will receive placebo and vice versa. The study ratio is 1:1. Dose of oxytocin is based upon previous studies in humans showing improvement in schizophrenia related changes in behavior and brain function (Kosfeld et al, 2005; Kirsch 2005; Heinrich M 2003).
The total study duration for each individual subject will be approximately 7 weeks, which includes up to 7-day screening period, a baseline (randomization) visit, three week treatment period, 1 week washout, baseline, and three weeks cross over treatment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult men or women, 18 years of age or older.
- •Meet DSM-IV criteria for Schizophrenia.
- •Women of childbearing potential must test negative for pregnancy at the time of enrollment based on urine pregnancy test and agree to use a reliable method of birth control during the study.
- •Must be on a therapeutic dose of an atypical antipsychotic medication (examples but not limited to Clozapine Olanzapine, Risperidone, Ziprasidone, Aripiprazole, Seroquel) with no major dose changes for at least 4 weeks.
- •A minimum PANSS total score of 55 at screening and baseline and a score of at least 4 (moderate) on the subscale of the PANSS (suspiciousness/persecution) at screening.
- •Have a Clinical Global Impressions-Severity (CGI-S) scale score of at least 4 (moderately ill) at baseline.
- •Must be able to communicate effectively with the investigator and study coordinator and have the ability to provide informed consent.
- •Must be able to use nasal spray.
- •Must demonstrate an acceptable degree of compliance with medication and procedures in the opinion of the investigator.
排除标准
- •Subjects will be excluded from the study of they meet any of the following criteria:
- •Are pregnant or are breastfeeding (negative pregnancy test at screening).
- •A urine drug screen performed at screening must not show evidence of recent use of drugs of abuse.
- •Any active medical condition that in the opinion of the investigator will interfere with the objectives of the study.
- •Are unsuitable in any way to participate in this study, in the opinion of the investigator.
- •Another current DSM-IV diagnosis other than Schizophrenia.
- •Subjects on one SSRI, and/or sleep medication (diphenhydramine, zolpidem, zaleplon, or diazepam), at a reasonable dose, as judged by the investigator, is permitted in this study.
研究组 & 干预措施
Group 2
Group 2: 3 week placebo trial, 1 week washout, 20 IU BID for the first week, 40IU BID for the following two weeks.
干预措施: Placebo (Drug)
Group 1
Group 1: 20 IU BID for the first week, 40IU BID for the following two weeks, 1 week washout, 3 week placebo trial.
干预措施: Oxytocin (Drug)
Group 1
Group 1: 20 IU BID for the first week, 40IU BID for the following two weeks, 1 week washout, 3 week placebo trial.
干预措施: Placebo (Drug)
Group 2
Group 2: 3 week placebo trial, 1 week washout, 20 IU BID for the first week, 40IU BID for the following two weeks.
干预措施: Oxytocin (Drug)
结局指标
主要结局
Total Score in the Positive and Negative Syndrome Scale (PANSS)
时间窗: performed at each visit (weekly)
次要结局
- Clinical Global Impression-Global Improvement(Performed at Visits 2-8 (weekly))
- Clinical Global Impression-Severity of Illness(performed at each visit (weekly))
- Letter Number Sequencing Memory Test(Visits 1, 4, and 8 (every 4 weeks))
- Calgary Depression Scale for Schizophrenia(performed at each visit (weekly))
- Global Assessment of Functioning(performed at each visit (weekly))
- Reading Trust in the Eyes Test (RTET)(Visits 1, 4, 5 and 8 (every 4 weeks))
- California Verbal Learning Test-Second Edition(Visits 1, 4, and 8 (every 4 weeks))
- Profile of Mood States(Visits 1 and 5 (first visit and 5 weeks later))
- Paranoid Thought Scale(Visits 1-8 (weekly))
- Hamilton Anxiety Scale(performed at each visit (weekly))
- Peabody Picture Vocabulary Test(Visit 1 only)
- Arizona Sexual Experience Scale (ASEX)(Visits 1-8 (weekly))
研究者
David Feifel
Professor
University of California, San Diego