Augmentation of Antipsychotics With L-Dopa (Sinemet)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- SANS - Schedule for the Assessment of Negative Symptoms
研究概览
简要总结
Dopamine, a chemical in the brain, has been linked to schizophrenia for a number of years. More recently, there is evidence that certain areas affected in schizophrenia (e.g. motivation, cognition) may reflect too little dopamine, whereas symptoms like hallucinations and delusions have been linked to too much dopamine.
This study is designed to evaluate the safety, tolerability, and efficacy of giving L-dopa (Sinemet) to see if it will improve those symptoms related to too little dopamine. L-dopa has been approved for other medical conditions (e.g. Parkinson's disease) and works to increase levels of dopamine.
The investigators are linking this study with neuroimaging (fMRI) which will allows us to link any changes the investigators might find in clinical symptoms with changes in the brain. This information can prove useful in better understanding the mechanisms that account for these symptoms, as well as possible new treatments.
At present , treatments for these other symptoms that seem important in functional measures of outcome (i.e. deficit symptoms, including amotivation; cognitive symptoms) in schizophrenia have not proven particularly effective. It is hoped that L-dopa may provide a treatment that is more effective; going forward, this information would also be useful in drug development and future lines of investigation.
- L-dopa will prove effective in improving deficit (also called 'primary negative' e.g. amotivation) and cognitive symptoms in schizophrenia.
- It will be well tolerated and not increase risk of psychotic symptoms when administered in conjunction with their regular antipsychotic medications.
详细描述
Pharmacological (and non-pharmacological) strategies that may significantly improve the negative and cognitive symptoms of schizophrenia represent a critical unmet therapeutic need. There is wide acceptance of the notion that both negative and cognitive symptoms are best understood as features of hypo- rather than hyperdopaminergic activity. The primary negative and cognitive symptoms appear central to schizophrenia and predate the neurodevelopmental changes that subsequently give rise to the hyperdopaminergic state underlying positive symptoms. In using L-Dopa specifically, we avoid the abuse potential of agents such as the psychostimulants, or perturbations in pharmacological action as a function of dose, as observed with dopamine agonists. Further, more recent neuroimaging studies have provided in vivo evidence in keeping with the underlying rationale. First, imaging studies have demonstrated that L-dopa induces shifts in activity in both cortical and subcortical structures linked to reward, affect and cognition. Along similar lines, L-dopa-induced changes have been associated with improvement in motivation, cognitive tasks, and affect.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis of schizophrenia
- •ages 18-55
排除标准
- •history of substance abuse or dependence within 3 months; (ii) positive urine drug screen
- •history or evidence of any disorder that might adversely influence cognitive measures (e.g. mental retardation)
- •presence of serious neurological or general medical condition (e.g., Parkinson's disease, cardiac arrhythmia, epilepsy)
- •clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease, narrow-angle glaucoma, malignant melanoma
- •pregnancy/nursing or women of child-bearing age not on regular contraceptive therapy (effects of L-dopa unknown)
研究组 & 干预措施
L-Dopa (Sinemet)
Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks
干预措施: levodopa/carbidopa (generic version of Sinemet) (Drug)
结局指标
主要结局
SANS - Schedule for the Assessment of Negative Symptoms
时间窗: 8 weeks
次要结局
- SAPS - Schedule for the Assessment of Positive Symptoms(8 weeks)
- NIMH-MATRICS Brief Negative Symptoms Scale(8 weeks)
- BIS-11 - Barrett Impulsivity Scale(8 weeks)
- SAS - Simpson Angus Scale for Extrapyramidal Symptoms(8 weeks)
- CGI-S - Clinical Global Impression - Severity Scale(8 weeks)
- QLS - Quality of Life Scale(8 weeks)
- CDS - Calgary Depression Scale(8 weeks)
- AIMS - Abnormal Involuntary Movement Scale(8 weeks)
- UKU - Udvalg for Kliniske Undersogelses(8 weeks)
- LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale(8 weeks)
- Y-BOCS - Yale-Brown Obsessive Compulsive Scale(8 weeks)
- DAI - Drug Attitude Inventory(8 weeks)
- BPRS - Brief Psychotic Rating Scale(8 weeks)
- fMRI - Functional Magnetic Resonance Imaging(8 weeks)
- MATRICS-Consensus Cognitive Battery(8 weeks)
- BARS - Barnes Akathisia Rating Scales(8 weeks)
- SWN - Subjective Well-Being on Neuroleptics Scale(8 weeks)
研究者
George Foussias
Sub-Investigator
Centre for Addiction and Mental Health