Effects of Varenicline on Brain Activity During Nicotine Abstinence

Study Overview
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Brief Summary
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This project aims to define mechanisms through which varenicline might be an effective smoking cessation medication.

Detailed Description
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Thirty treatment seeking smokers will be recruited to complete a 40-day within-subject (cross-over), double-blind study that will assess effects of varenicline on brain activation while performing certain tasks. Prior to beginning the study, participants will complete an health and physical screening to determine final eligibility. Following a medication run-up and a 3.5 day abstinence period, participants will complete study period 1 (an fMRI scan while performing attention, working memory and emotion tasks). After a 14 to 21-day washout period the study procedures will be repeated with placebo (order of study medication counterbalanced). After completion of both study periods, all participants will be offered a 13-week quit smoking program with varenicline.

Official Title
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Neural Substrates of Varenicline's (Chantix®) Efficacy for Smoking Cessation

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: Treatment-seeking smokers between the ages of 18 and 65, that smoke at least 10 cigarettes/day for at least the past 6 months Provide a baseline CO (carbon monoxide) reading of >10ppm Provide written informed consent and are fluent, English-speaking Weight of equal to or less than 300 lbs Exclusion Criteria: Smoking Behavior Use of chewing tobacco, snuff or cigars Current enrollment or plans to enroll in another smoking cessation program in the next 5 months Plan to use other nicotine substitutes or smoking cessation treatments in the next 5 months Provide a baseline CO (carbon monoxide) reading ≤10 ppm Alcohol/Drug Exclusion Criteria History of substance abuse and/or currently receiving treatment for substance abuse Current alcohol consumption that exceeds 25 standard drinks/week A breath alcohol concentration reading ≥ 0.01 at the H&P (health & physical) screening or either of the lab sessions Medication Exclusion Criteria Prior use of Chantix Current use or recent discontinuation (within last 14-days) of the following medications: Any form of smoking cessation medication Any form of anti-psychotic medications that includes: antipsychotics, atypical antipsychotics, mood-stabilizers, anti-depressants (tricyclic, SSRI, MAOI), anti-panic agents, anti-obsessive agents, anti-anxiety agents, and stimulants (e.g., Provigil, Ritalin) herbal medications (St. John's Wort) Opioid medication for chronic pain Anti-coagulants Any heart medications Daily medication for asthma Medical Exclusion Criteria Women who are pregnant, planning a pregnancy, or lactating; History or current diagnosis of psychosis, current major depression, bipolar disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI Serious or unstable disease within the past 6 months (heart disease, HIV) Diagnosis of cancer in the past 6 months or if successful treatment for cancer has not ended within the past 6 months History of epilepsy or a seizure disorder History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of COPD (chronic obstructive pulmonary disease), cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90) History of kidney and/or liver failure (including transplant) History of head trauma or prior seizure; family history of a seizure disorder, brain (or central nervous system) tumor Use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI (magnetic resonance imaging); Low or borderline intellectual functioning - determined by receiving a score <80 on the Shipley verbal IQ Test Non-English speaking; determined at phone screen History of claustrophobia (contraindicated for MRI) or color blindness (task requires color recognition); self-report at telephone screen Being left-handed Any fore-limb deformity Wearing cochlear implant or bi-lateral hearing aids General Exclusion Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician. Any physical or visual impairment that may prevent the individual from using a computer keyboard or completing any study tasks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants will take placebo pills for 13 days using the same regimen as the varenicline study period.<br>|
| Active Comparator: Varenicline<br> | Drug: Varenicline<br>* Day 1 - Day 3 0.5mg once daily Day 4 - Day 7 0.5mg twice daily Day 8 - Day 13 1.0mg twice daily<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change BOLD Signal | We calculated the percent BOLD signal change while performing the N-back task between the varenicline vs. placebo session. We subtracted BOLD signal observed during the 0-back condition from the BOLD signal observed during the 3-back condition (3back minus 0-back)We controlled for relevant co-variates such as sex, nicotine dependence level and education. | Day 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) | We examined the difference in correct reaction time on the N-back task between varenicline and placebo treatment. Models included terms for the main effect of treatment period (varenicline vs. placebo), memory load (0-back, 1-back, 2-back, 3-back) and covariates. We tested for interactions between nicotine dependence severity and treatment. | Day 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Varenicline, Imaging, fMRI