Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
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|ClinicalTrials.gov Identifier: NCT01093365|
Recruitment Status : Completed
First Posted : March 25, 2010
Last Update Posted : August 26, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Schizophrenia Schizoaffective Disorder||Drug: Varenicline||Phase 2|
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).
All groups will be age- and sex- matched. Pre-treatment with varenicline (VAR) or placebo will start on Day 1 of each test session will be as follows: 1) 0.0 mg/day 2) 0.5 mg twice daily 3) or 1 mg twice daily for 3 days. Testing days will be separated by at least 1 week apart to rule out medication carry-over effects.
If nicotinic acetylcholine receptors can be stimulated resulting in more dopamine release and improved neurocognitive function without inducing deleterious health effects it may be of benefit to persons with schizophrenia who smoke tobacco.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||58 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia|
|Study Start Date :||March 2010|
|Actual Primary Completion Date :||August 2016|
|Actual Study Completion Date :||August 2016|
To measure the effects of varenicline on cognition of smokers with schizophrenia.
- Computerized testing of neuropsychological functioning [ Time Frame: 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 [ Time Frame: Three times per week for three consecutive weeks ]
- Minnesota Withdrawal Scale [ Time Frame: Three times over a two day period for three consecutive weeks ]
- Pre-pulse inhibition [ Time Frame: 3 times per week for 3 weeks ]Measurement of startle reactivity to tones by EMG and the inhibition of the EMG response by exposure to a "pre-pulse".
- Smoking topography [ Time Frame: 3 times a week for 3 weeks ]Topographic assessment of smoking behavior (e.g., number of puffs per cigarette, puff volume, amount of time between puffs)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01093365
|Centre for Addiction and Mental Health (33 Russell street)|
|Toronto, Ontario, Canada, M5S 2S1|
|Principal Investigator:||Tony P George, MD||Centre for Addiction and Mental Health|