A Randomized Trial Administering Oxytocin vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia and Schizo-affective Disorder
试验速览
- 阶段
- 2 期
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Total score of structured assessment of social interaction
研究概览
简要总结
The objectives of the study are:
- To evaluate the effect of OT compared to placebo, as add-on to anti-psychotics, on social functioning in schizophrenia.
- To evaluate the effect of socially oriented CBT administered to patients immediately after they receive OT, compared to patients who receive OT with not-socially oriented CBT, and compared to patients who receive socially oriented CBT without OT. The investigators hypothesize that OT and socially oriented CBT will have a synergistic effect, and will be better than OT or CBT alone.
- Use a detailed, in depth analysis of social interaction to assess these putative effects of OT. The investigators hypothesize that the use of this analysis will show larger treatment effects of OT than previously shown in less sensitive assessments, such as PANSS.
- To assess the effect of epigenetic status on response to OT. The investigators hypothesize that epigenetic variants associated with lower OT plasma levels will be associated with greater response to OT treatment.
- To assess in the relationships between levels of salivary OT and vasopressin, and social interactions in schizophrenia.
- To assess in the relationships between levels of salivary OT and vasopressin, and response to OT treatment.
详细描述
Social disability is a hallmark of schizophrenia, and improving social functioning in schizophrenia should improve patients' overall functioning and quality of life. Oxytocin (Granholm, McQuaid et al.) is a nine amino-acid neuropeptide synthesized in the hypothalamus, has found to modulate social behaviors in mammals, including humans (Insel and Young 2001; Kosfeld, Heinrichs et al. 2005). Among its influences on human social behavior are increased trust (Kosfeld, Heinrichs et al. 2005), empathy (Hurlemann, Patin et al. 2010) and eye contact (Guastella, Mitchell et al. 2008).
Impaired social behaviors are a core domain of Autism Spectrum Disorders (ASD) (Modahl, Green et al. 1998; Bartz and Hollander 2008); studies have shown that social disabilities have been associated with OT dysfunction in ASD, and have been improved by administration of intranasal OT (Hollander, Bartz et al. 2007; Andari, Duhamel et al. 2010; Guastella, Einfeld et al. 2010).
Furthermore, epigenetic changes in the genes encoding for OT have been demonstrated in autism (Gregory, Connelly et al. 2009)
Impaired social functioning is a hallmark of schizophrenia; studies show that plasma levels of endogenous OT are lower in schizophrenia patients compared to controls, and patients with lower levels of plasma OT have more positive symptoms (Kéri , Kiss et al. 2009; Kיri, Kiss et al. 2009; Rubin, Carter et al. 2010). Moreover, a recent study demonstrated a significant genetic association between OT and Arginine Vasopressin, another peptide linked with social behavior, and schizophrenia (Teltsh, Kanyas-Sarner et al. 2011). Only two published studies have investigated the therapeutic potential of OT in schizophrenia; both administered OT in addition to anti-psychotic treatment. Feifel (Feifel, Macdonald et al. 2010) reported a decrease in positive symptoms after 3 weeks of treatment, and Pedersen (Pedersen, Gibson et al. 2011) reported an improvement in social cognition. There is ongoing research aiming to validate these findings.
Vasopressin is also a peptide with a putative effect on social interaction (Ebstein, Israel et al. 2009; Heinrichs, von Dawans et al. 2009). In this proposed study we will assay salivary levels both of OT and vasopressin.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-65 years of age, inclusive
- •Females who are abstinent or practicing an established method of birth control (oral contraceptive tablets, hormonal implant device, hormone patch, injectable contraceptive, intrauterine device [IUD]).
- •Willing and able to provide informed consent, after the nature of the study has been fully explained
- •Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified SCID.
- •Symptoms: PANSS total score ≤75
- •A score of 4 (moderate) or higher on at least one, or more of the following PANSS negative items: emotional withdrawal, poor rapport, passive-apathetic social withdrawal
- •Receiving the same antipsychotic medication for 2 weeks before randomization.
- •Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission, provided no medication change since hospitalization.
- •Adjunctive treatment with anticholinergic agents, beta-blockers, mood stabilizers, antidepressants; and anxiolytics will be allowed provided that patients have been on the medication for at least 2 weeks prior to entry into the screening phase of the study.
排除标准
- •Unwilling or unable, in the opinion of the Investigator, to comply with study instructions.
- •Pregnant or breast-feeding.
- •Clinically significant medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning).
- •At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
- •Patients with a current DSM-IV substance or alcohol abuse. Patients with a history of and/or current recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
- •Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
- •Patients with significantly impaired renal or liver function, defined as GOP and or GPT levels >3 times above highest normal value, and or blood creatinine levels above 1.5 will be excluded.
研究组 & 干预措施
Oxytocin + Social Skills training
干预措施: Oxytocin (Drug)
Oxytocin + Social Skills training
干预措施: Social Skills Training (Behavioral)
Oxytocin+ Non Specific Counselling
干预措施: Oxytocin (Drug)
Placebo + Non Specific Counselling
干预措施: Placebo + Non Specific Counselling (Behavioral)
Placebo + Social Skills Training
干预措施: Social Skills Training (Behavioral)
结局指标
主要结局
Total score of structured assessment of social interaction
时间窗: Baseline and week 3
Change from baseline in the total score of structured assessment of social interaction in Oxytocin compared with placebo on all patients.
次要结局
- Total score of structured assessment of social interaction(Total score of structured assessment of social interaction at week 3)
- PANSS positive, negative and general psychopathology scales scores(PANSS positive, negative and general psychopathology scales scores at week 3)
- Total score of structured assessment of social interaction and PANSS scores, genetic and epigenetic status(Total score of structured assessment of social interaction and PANSS scores, genetic and epigenetic status at week 3)
- Levels of salivary OT,genetic,epigenetic status and total score of structured assessment of social interaction and PANSS scores.(Levels of salivary OT,genetic and epigenetic status at week 3)