A Randomised, Double Blind Pilot Study of Minocycline and Placebo Added to Treatment-as-Usual (TAU) in First-Episode Psychosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 4
- 主要终点
- Positive and negative symptoms on Positive and Negative Syndrome Scale (PANSS)
研究概览
简要总结
The purpose of this study is to determine whether the addition of minocycline or placebo to treatment as usual (TAU):
- prevents the accumulation of negative symptoms and intellectual decline following a first episode of non-affective psychosis; and
- whether minocycline stabilizes the efficacy of antipsychotics.
详细描述
Background:
There is increasing clinical, neuropsychological and imaging evidence that schizophrenia involves a progressive process at the time of the first episode and later in life. However, it is not clear which systems are affected nor in which parts of the brain. In two Stanley first episode cohorts at Manchester (Stirling et al, 2004,) and in a group of elderly patients with schizophrenia (Gabrovska-Johnson et al 2004), evidence of deterioration in visuo-spatial functions has been found. This implies a right-hemisphere pathology. Other evidence suggests that the initiation of schizophrenia may involve left-sided pathology (Lawrie et al 2002) so it could be that right hemisphere pathology may follow left and give rise to the deficits of chronic schizophrenia (Gabrovska-Johnson et al 2004). If so, early treatment with a neuroprotective agent might prevent the accumulation of deficit symptoms and cognitive impairment.
Minocycline is a tetracycline antibiotic with proven long-term high dose safety in humans, is routinely used to treat acne and rheumatoid arthritis demonstrating that it acts as a non-steroidal anti-inflammatory, as well as an antimicrobial drug. Minocycline, unlike tetracycline, crosses the blood-brain barrier. This and related compounds show neuroprotective properties in rat models of ischemic brain damage, in glutamate neurotoxicity in cell cultures and in a rat model of Huntington's disease in which it slowed progression (Chen et al, 2000; Yrjanheikki et al, 1999). Minocycline delays disease onset and extends survival in amyotrophic lateral sclerotic mice (Shan Zhu et al 2002).
Minocycline has various properties including inhibition of capsases, inhibition of microglial activation, reduced cyclooxygenase-2 expression and reduced prostaglandin E (2) formation. Furthermore, it inhibits the formation of inducible nitric oxide - a mechanism of glial activation. All these mechanisms have been implicated in schizophrenia. All these mechanisms have been implicated in schizophrenia.
Because of its broad spectrum of action, we consider minocycline is an important candidate molecule for the prevention of deterioration in schizophrenia. Based on the evidence so far we propose a randomised double blind placebo controlled study of minocycline added to treatment-as-usual (TAU) in first-episode psychosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- Double
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
- •Aged 18 to 65 years
- •Diagnostic and Statistical Manual-IV (DSM-IV) diagnosed first episode psychosis, schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder
- •First episode (within first 5 years of diagnosis)
- •Competent and willing to give informed consent
- •Medication remained stable 4 weeks prior to baseline
- •Able to take oral medication and likely to complete the required evaluations
- •Female participants of child bearing capability must be willing to use adequate contraceptives for the duration of the study, and, willing to have a pregnancy test pre-treatment and at ten weekly intervals while on study medication
排除标准
- •Relevant medical illness [renal, hepatic, cardiac, serious dermatological disorders such as exfoliative dermatitis, systemic lupus erythematosus (SLE)] in the opinion of the investigators (see section 6.2a)
- •Prior history of intolerance to any of the tetracyclines
- •Concomitant penicillin therapy
- •Concomitant anticoagulant therapy
- •Presence of a seizure disorder, not including clozapine-induced seizures
- •Presently taking valproic acid
- •Any change of psychotropic medications within the previous six weeks
- •Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria
- •Pregnant or breast-feeding
研究组 & 干预措施
Minocycline
干预措施: Minocycline (Drug)
Sugar Pill
干预措施: Placebo (Drug)
结局指标
主要结局
Positive and negative symptoms on Positive and Negative Syndrome Scale (PANSS)
时间窗: Baseline and 12 months
次要结局
- neurocognitive test scores(Baseline and 12 months)
- Assessment of side effects(Baseline and 12 months)
- Doses of antipsychotic drugs(Baseline and 12 months)
- Global Assessment of Functioning (GAF)(Baseline and 12 months)
- Clinical Global Impression (CGI)(Baseline and 12 months)
- Abnormal Involuntary Movement Scale (AIMS)(Baseline and 12 months)