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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
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Tony George, Centre for Addiction and Mental Health

Tracking Information
First Submitted Date  ICMJE March 24, 2010
First Posted Date  ICMJE March 25, 2010
Last Update Posted Date August 26, 2016
Study Start Date  ICMJE March 2010
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2010)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01093365 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2011)
  • 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)
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
Official Title  ICMJE Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia
Brief Summary

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.

Detailed Description

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:

  1. cigarette smokers with schizophrenia (N=10),
  2. non-smokers with schizophrenia (N=10),
  3. healthy cigarette smoking controls (N=10),
  4. 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Schizophrenia
  • Schizoaffective Disorder
Intervention  ICMJE Drug: Varenicline
  • 0.0 mg orally twice per day for three days (placebo)
  • 0.5 mg orally twice per day for three days
  • 1.0 mg orally twice per day for three days
Other Names:
  • Chantix
  • Champix
Study Arms  ICMJE Experimental: Schizophrenia
To measure the effects of varenicline on cognition of smokers with schizophrenia.
Intervention: Drug: Varenicline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 25, 2016)
58
Original Estimated Enrollment  ICMJE
 (submitted: March 24, 2010)
40
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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:

  1. 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)
  2. 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)

Exclusion Criteria:

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01093365
Other Study ID Numbers  ICMJE 067/2009
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tony George, Centre for Addiction and Mental Health
Study Sponsor  ICMJE Centre for Addiction and Mental Health
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Tony P George, MD Centre for Addiction and Mental Health
PRS Account Centre for Addiction and Mental Health
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP