Effects of Varenicline on Smoking Lapse in Smokers With and Without Schizophrenia
Information source: Centre for Addiction and Mental Health
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Craving; Smoking; Schizophrenia.
Intervention: Varenicline (Drug); Placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Centre for Addiction and Mental Health Official(s) and/or principal investigator(s): Tony George, M.D., Study Director, Affiliation: Centre for Addiction and Mental Health
Summary
The objective of this study is to determine the mechanisms by which varenicline, an
effective smoking cessation treatment, protects against relapse. Varenicline will be
administered in smokers with schizophrenia and control smokers using a randomized,
double-blind, cross-over design. Smokers will be asked to stop smoking overnight; the next
day the ability to resist smoking will be assessed in a laboratory smoking lapse paradigm.
Measures of tobacco craving, reinforcement and withdrawal-related cognitive dysfunction will
be correlated with time to lapse. The results could have significant clinical implications
by identifying mechanisms by which smokers with schizophrenia are at more risk for relapse
than the general population, leading to the development of more effective smoking cessation
therapies.
Clinical Details
Official title: Evaluating the Effects of Varenicline on Smoking Lapse in Smokers With and Without Schizophrenia: Implications for Treatment
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary outcome: Time to Lapse
Secondary outcome: Cognitive FunctionTobacco craving Tobacco withdrawal Tobacco Reinforcement
Detailed description:
One way to facilitate medication development for smoking cessation is through the use of
human laboratory paradigms that can provide an efficient, cost-effective and mechanistic
evaluation of a medication signal on smoking behavior and bridge pre-clinical studies and
costly clinical trials. This study will take advantage of the recent development and
validation of a smoking lapse procedure to evaluate the effects of varenicline in smokers
with and without schizophrenia. We will extend our recent work with varenicline by relating
its effects on reinforcement, craving and cognition to clinical outcome (i. e., lapse - a
strong predictor of relapse). It is pertinent to study smokers with schizophrenia because as
smoking rates decline in the general population we will be left with a group of'hardcore'
smokers for whom current smoking cessation strategies have limited efficacy.
The objective of this study is to determine the effect of varenicline versus placebo, on
time to lapse, as a function of craving, reinforcement and cognitive dysfunction, in smokers
with and without schizophrenia. We hypothesize that:
1. Smokers with schizophrenia will have reduced ability to resist smoking during the
placebo condition compared to controls; and secondarily, this will be related to the
higher levels of cognitive dysfunction during abstinence.
2. Varenicline will increase the ability to resist smoking in both control and
schizophrenia smokers; and secondarily, this will be mediated via its effects on
cognition in smokers with schizophrenia, and its effects on craving in control smokers.
The exploratory aims are to determine:
1. Varenicline's effect on cue-reactivity in smokers with and without schizophrenia and
its relationship to time to lapse.
2. Varenicline's effects on tobacco reinforcement and its relationship to ad lib smoking
in the lapse period
The current study will advance the development of tobacco addiction treatments in the
following ways: 1) Identification of mechanisms by which varenicline facilitates abstinence
in different subtypes of smokers (schizophrenia vs. controls) is critical to improve
treatment response. 2) Identification of predictors of relapse in different subtypes of
smokers (schizophrenia vs. controls) could guide future medication development efforts. 3)
Relating measures of tobacco abstinence and addiction collected in the laboratory to proxy
measures of treatment outcome (i. e., smoking lapse) will provide further validation that
evaluation of medications in such paradigms is a useful and cost-effective screening
strategy. 4) Our approach could also be used to identify smokers most at risk for tobacco
abstinence symptoms who would benefit from treatments targeting the most prominent aspects
of withdrawal. This could lead to improved health outcomes in smokers.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Cigarette Smokers (smoke ≥ 10 cigarettes per day)
- non-treatment seeking (i. e., not trying to quit as indicated by <7 on the
contemplation ladder)
- aged 18-55
- Intelligence Quotient (IQ) ≥80 on the Wechsler Test of Adult Reading [89]
- Fagerstrom Test of Nicotine Dependence (FTND) ≥4 [90]
- Patients must meet Structured Clinical Interview for the diagnostic and Statistical
Manual for Mental Disorders (SCID-IV) diagnosis criteria for schizophrenia or
schizoaffective disorder; be in stable remission from positive symptoms of psychosis
as judged by a Positive and Negative Syndrome Scale (PANSS) positive score total
score <70, and receiving a stable dose of antipsychotics for >1month.
- Control participants will not be taking any psychotropic medications at the time of
enrollment and will not meet diagnostic criteria for any Axis I disorder, except past
history of major depression or an anxiety disorder if in remission for at least one
year.
Exclusion Criteria:
- substance use (except nicotine or caffeine) in the last month
- a history of alcohol/drug abuse in the 3 months before study enrollment
- use of opioids (meperidine, oxycodone, methadone, etc)
- current use of smoking cessation aids (e. g., nicotine replacement therapy, bupropion
or varenicline
- pregnancy or nursing
- a history of renal insufficiency or a hypersensitivity to varenicline (Champix®)
- a history of neurological illness like epilepsy or medical condition known to
significantly influence neurocognitive function
- any other medical condition deemed relevant by the Qualified Investigator.
Locations and Contacts
Centre for Addiction and Mental Health, Toronto, Ontario M5S 2S1, Canada
Additional Information
Information about research at the Centre for Addiction and Mental Health
Starting date: June 2013
Last updated: July 9, 2015
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