Effect of Varenicline on Cognitive Function in Cigarette Smokers With Schizophrenia

NCT01093365 | Completed Phase 2 DMC

• 1 other identifier: 067/2009
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; Schizoaffective Disorder; Varenicline; Champix; Chantix; Nicotine; Nicotinic receptor; Dopamine; Acetylcholine; Cigarette; Smoking; Tobacco; Executive function; Working memory; Verbal memory; Cognitive function; Neuropsychological function

Outcome Measures

Primary Outcomes (3)

• Computerized testing of neuropsychological functioning

  * 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)

  Three times per week for three consecutive weeks

• Tiffany Urge to Smoke Scale

  Three times per week for three consecutive weeks

• Minnesota Withdrawal Scale

  Three times over a two day period for three consecutive weeks

Secondary Outcomes (2)

• Pre-pulse inhibition

  3 times per week for 3 weeks

• Smoking topography

  3 times a week for 3 weeks

Study Arms (1)

Schizophrenia

EXPERIMENTAL

To measure the effects of varenicline on cognition of smokers with schizophrenia.

Drug: Varenicline

Interventions

Varenicline DRUG

* 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

Also known as: Chantix, Champix

Schizophrenia

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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
• No diagnosis for any Axis I psychiatric disorder (Except past history of major depression)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Pfizer: collaborator

Study Sites (1)

Centre for Addiction and Mental Health (33 Russell street)

Toronto, Ontario, M5S 2S1, Canada

Location

Related Publications (1)

• Johnstone S, Sorkhou M, Rabin RA, George TP. Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia. Drug Alcohol Depend. 2022 May 1;234:109412. doi: 10.1016/j.drugalcdep.2022.109412. Epub 2022 Mar 28.

  PMID: 35395548 DERIVED

Related Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital. It is fully affiliated with the University of Toronto, and is a PAHO/WHO Collaborating Centre

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Smoking

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Study Officials

• Tony P George, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director, Schizophrenia Program

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 25, 2010
• Study Start: March 1, 2010
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 26, 2016

Record last verified: 2016-08

Locations

CA (1)