Effects of Varenicline on Smoking Reminders

Study Overview
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Brief Summary
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Varenicline is the best smoking cessation agent to date; however it is only effective in a subgroup of smokers and is associated with undesirable side effects in other subgroups. To understand the underlying pharmaco-heterogeneity, the proposed project will use perfusion functional magnetic resonance imaging and a functional candidate gene association approach using brain, behavioral, and clinical endpoints in a placebo-controlled study of chronic varenicline administration in smokers. Brain and behavioral responses to smoking cues will be will be significantly greater in 9/10-repeats compared to 10/10-repeats. DAT 9/10-repeat smokers receiving varenicline will have better treatment outcome compared to 10/10-repeats. For the purposes of the clinical trial portion of the study, the change from cigarettes per day at Baseline to the last day of treatment will be reported.

Official Title
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Characterizing a Cue-vulnerable Pharmaco-responsive Endophenotype in Smokers

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Varenicline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physically healthy male or female nicotine dependent patients ages 18-60 without other current drug dependence or psychiatric diagnosis. Smoke ≥ 10 cigarettes per day for at least 6 months prior to study start date. Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control from at least 2 weeks prior to screening until 30 days after the last dose of varenicline. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine (IUD), oral contraceptives, levonorgestrel implant, or complete abstinence. Subjects provide voluntary informed consent. Subjects must read at 8th grade level or higher. Exclusion Criteria: History of head trauma or injury causing loss of consciousness, lasting more than three (3) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI. Presence of magnetically active prosthetics, plates, pins, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body. Self report of HIV positive and on medication for symptoms: Determined on an individual basis by results from the physical examination and final approval by the study physician. Symptomatic presence of other hematological disease. Clinically significant hepatic (liver), renal (kidney), neurological, or endocrinological abnormalities. History of any cardiovascular event within the last 6 months and any serious/significant cardiovascular event in the subject's life. This will be determined on an individual basis by the study physician. History of psychosis or seizures. Use of medications or natural herbs that may cause sedation or may effect the brain systems that are being studied (medication use will be evaluated on a case-by-case basis). Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Group<br>Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks. | Drug: Placebo<br>* Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.<br>* Other names: Sugar Pill;|
| Active Comparator: Varenicline<br>Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks. | Drug: Varenicline<br>* Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarettes Per Day | Cigarettes per day at Baseline versus 8 weeks of treatment, placebo-controlled | last week of treatment (1-8 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smokers, fMRI, varenicline