A Dose-response Study of Modafinil Effects on Cognition in Schizophrenia Patients.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Cognitive Performance
研究概览
简要总结
Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This includes many types of cognitive dysfunction, such as in attention, memory and language. These problems may explain why patients with schizophrenia think and act in unusual ways, and often have problems managing aspects of their lives that healthy adults take for granted. Unfortunately, the biochemical aspects of these dysfunctions are presently unknown, and it is not clear whether current psychiatric medications can improve these functions. A recent FDA-approved medication that may improve this function is modafinil. Studies in animals and healthy adults show that this medication can improve many of these cognitive functions. We plan to study the effects of modafinil on these cognitive processes, by giving various doses of this medication to patients before they perform tasks of these cognitive processes. We predict that when patients receive modafinil, they will perform better on a cognitive test, and that these benefits will depend on the dose given.
详细描述
Schizophrenia is a disorder of cognition. The cognitive deficits of schizophrenia are present at the onset of the disorder, prior to medication exposure, are persistent during periods of remission, and are strongly related to functional outcome. These deficits prominently include prefrontal cortex-dependent functions. While existing medications effectively treat psychotic symptoms, they exhibit modest benefit at best for cognitive dysfunction. Studies of cognition in animal models indicate that the neurotransmitter systems that mediate many cognitive processes are not generally augmented by existing antipsychotic medications. Therefore, advances in the treatment of schizophrenia will require the study of agents with novel pharmacological profiles to establish their potential to remediate cognitive dysfunction.
This study will evaluate the effects of modafinil on the range of cognitive processes known to be disturbed in schizophrenia. Modafinil is an FDA-approved medication with a unique pharmacological profile and an increasing range of off-label indications. Its neurochemical effects in animal models include elevation of extracellular dopamine (DA), noradrenaline (NA) and glutamate in the neocortex. This profile is favorable for the enhancement of cognitive processes. These neurochemical effects also appear to be selective for cortical versus subcortical brain regions, suggesting that modafinil may have minimal effects on psychotic symptoms, or extrapyramidal, autonomic and hormonal side effects. In addition, it differs from amphetamine in structure, neurochemical profile and behavioral effects, with a lower risk of addictive or cerebrovascular effects. Recent studies in animal models, healthy adults and adults with psychiatric and neurological disorders indicate that modafinil improves prefrontal cognitive functions. This suggests that modafinil is a leading candidate for the treatment of cognitive dysfunction in schizophrenia. We aim to test modafinil effects on the remediation of deficits in cognition in individuals with schizophrenia. We will vary the dose within each participant to evaluate dose-response relationships, and directly compare cognition outcome measures for sensitivity to drug effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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 54 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •adults age 18-54
- •diagnosis of schizophrenia or schizoaffective disorder, or healthy with no personal or family history of mental illness
- •able to provide informed consent
排除标准
- •history of significant head injury or other neurological illness
- •active psychiatric illness requiring significant acute care
- •significant intellectual impairment (e.g. standardized full-scale IQ < 70)
- •history of medical illness or treatment that is associated with significant increase in risk from modafinil treatment (e.g. cardiac disease)
- •significant active substance abuse
- •active pregnancy
- •active treatment with medications that have drug interactions with modafinil
研究组 & 干预措施
Placebo
Single oral placebo capsule
干预措施: modafinil (M1, M2, M4) (Drug)
100 mg
modafinil 100 milligrams oral dose
干预措施: modafinil (M1, M2, M4) (Drug)
200 mg
modafinil 200 mg oral dose
干预措施: modafinil (M1, M2, M4) (Drug)
400 mg
modafinil 400 mg oral dose
干预措施: modafinil (M1, M2, M4) (Drug)
结局指标
主要结局
Cognitive Performance
时间窗: 3-5 hours
Percent Accuracy on high-control (i.e. difficult) condition on test of cognitive control
次要结局
- Heart Rate(3-5 hours)
- Systolic Blood Pressure(3-5 hours)
研究者
Michael Minzenberg, MD
Associate Professor of Clinical Psychiatry
University of California, Davis