Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Computerized testing of neuropsychological functioning
研究概览
简要总结
Smokers with schizophrenia have more difficulties quitting smoking than smokers without a mental disorder. Varenicline (Champix) is a new stop smoking medication with a unique mechanism of action. It is a nicotine-like drug which is not addictive and not associated with the health risks of tobacco smoking.
Varenicline (VAR) binds to sites in the brain called nicotine receptors that play an important role in nicotine dependence. People with schizophrenia have difficulties in concentrating and remembering. Scientists believe that people with schizophrenia use smoking to remedy their cognitive problems. We will test VAR to see if it improves cognitive problems in smokers with schizophrenia in comparison to non-mentally ill smokers to determine whether people with schizophrenia get direct benefit from this nicotine-like drug. It is hypothesized that VAR (in comparison to a placebo) will reduce aspects of cognitive impairment in smokers and nonsmokers with schizophrenia.
详细描述
Schizophrenia is characterized by deficits in neurocognitive function, including executive function, attention, and spatial and verbal memory. Central nicotinic acetylcholine receptors (nAChR) are dysregulated in schizophrenia. It has been shown that neurocognitive deficits in schizophrenia improve by administration of nicotine, nicotinic agonists or cigarette smoking. Hence, it is believed that cigarette smoking may remedy cognitive deficits in schizophrenia and in fact some persons with schizophrenia may be "self-medicating" with tobacco to counter such cognitive problems.
The prevalence rates of cigarette smoking in persons with schizophrenia are higher than in the general population (58-88% vs. 25% respectively). This population also has a nicotine dependence rate of around 80 % and a high relapse rate after smoking cessation. Additionally the leading cause of medical problems and death in people with schizophrenia is tobacco addiction. Research that addresses the problem of smoking in schizophrenia is of great importance.
Varenicline (VAR), an α4β2 nAChR partial agonist, approved for smoking cessation, mimics the effect of nicotine by stimulating nAChRs, and releasing sufficient dopamine in order to reduce craving and withdrawal effects.
This study will follow four groups of subjects (N=40) that will receive neuropsychological and psychiatric testing in three consecutive sessions (smoking satiation, abstinence and reinstatement) separated by at least one week over 3 weeks. The groups are:
- cigarette smokers with schizophrenia (N=10),
- non-smokers with schizophrenia (N=10),
- healthy cigarette smoking controls (N=10),
- non-smoking controls (N=10).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •I) For all subjects
- •Age 18-55
- •Estimated IQ ≥80 using the Shipley scale
- •Capable of giving informed consent
- •Not taking any form of nicotine replacement therapy
- •II) Additional inclusion criteria for smokers:
- •Non-treatment seeking cigarette smokers:
- •A score of 5 or higher on the Fagerstrom Test for Nicotine Dependence (FTND)
- •Self reported smoking of at least 10 cigarettes per day as measured by the Weekly Smoking Inventory (NOTE: Cigarette smoking is verified by a Smokerlyzer® test, with a cut off of 10 ppm and plasma cotinine levels ≥150 ng/ml)
- •Cigarette smokers with Schizophrenia:
- •Diagnosis of schizophrenia/schizoaffective disorder (confirmed by the SCID for DSM-IV)
- •Stable remission from positive symptoms of psychosis as judged by a score of <70 on the The Positive and Negative Syndrome Scale (PANSS) for schizophrenia and a psychiatric evaluation
- •Receiving a stable dose of antipsychotic medication(s)for the past month
- •III) Additional inclusion criteria for healthy smokers and non-smokers:
- •No diagnosis for any Axis I psychiatric disorder (Except past history of major depression)
排除标准
- •For all subjects
- •Substance abuse other than cigarette smoking.
- •History of alcohol/drug abuse in the 3 months before study enrollment
- •Hypersensitivity to varenicline (Champix)
- •Use of opioids (meperidine, oxycodone, methadone, etc).
- •A history of renal insufficiency
- •Gastrointestinal problems including irritable bowel syndrome
- •Exposure to chemotherapy
- •A history of dementia and other neurological illness like epilepsy or medical condition known to significantly influence neurocognitive function
- •Inability to learn the neuropsychological tasks during the training session
- •Failure to demonstrate a deficit of at least 0.5 standard deviations below average levels of non-psychiatric control performance the on the Visuospatial Working Memory (VSWM) task
- •Pregnancy
- •Nursing women
研究组 & 干预措施
Schizophrenia
To measure the effects of varenicline on cognition of smokers with schizophrenia.
干预措施: Varenicline (Drug)
结局指标
主要结局
Computerized testing of neuropsychological functioning
时间窗: Three times per week for three consecutive weeks
* Trail Making Test, Part A * Trail Making Test, Part B * Visuospatial Working Memory (VSWM) and Digit Span of WAIS * Hopkins Verbal Learning Test - Revised (HVLT-V) * Continuous Performance Task (CPT)
Tiffany Urge to Smoke Scale
时间窗: Three times per week for three consecutive weeks
Minnesota Withdrawal Scale
时间窗: Three times over a two day period for three consecutive weeks
次要结局
- Smoking topography(3 times a week for 3 weeks)
- Pre-pulse inhibition(3 times per week for 3 weeks)
研究者
Tony George
Clinical Director, Schizophrenia Program
Centre for Addiction and Mental Health