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

18 Years
65 Years
Not Enrolling
Nicotine Dependence

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Trial Information

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

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.

Inclusion Criteria:

1. Treatment-seeking smokers between the ages of 18 and 65, that smoke at least 10
cigarettes/day for at least the past 6 months

2. Provide a baseline CO (carbon monoxide) reading of >10ppm

3. Provide written informed consent and are fluent, English-speaking

4. Weight of equal to or less than 300 lbs

Exclusion Criteria:

Smoking Behavior

1. Use of chewing tobacco, snuff or cigars

2. Current enrollment or plans to enroll in another smoking cessation program in the
next 5 months

3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 5

4. Provide a baseline CO (carbon monoxide) reading ≤10 ppm

Alcohol/Drug Exclusion Criteria

1. History of substance abuse and/or currently receiving treatment for substance abuse

2. Current alcohol consumption that exceeds 25 standard drinks/week

3. A breath alcohol concentration reading ≥ 0.01 at the H&P (health & physical)
screening or either of the lab sessions

Medication Exclusion Criteria

1. Prior use of Chantix

2. Current use or recent discontinuation (within last 14-days) of the following

1. Any form of smoking cessation medication

2. 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)

3. Opioid medication for chronic pain

4. Anti-coagulants

5. Any heart medications

6. Daily medication for asthma

Medical Exclusion Criteria

1. Women who are pregnant, planning a pregnancy, or lactating;

2. History or current diagnosis of psychosis, current major depression, bipolar
disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI

3. Serious or unstable disease within the past 6 months (heart disease, HIV)

4. Diagnosis of cancer in the past 6 months or if successful treatment for cancer has
not ended within the past 6 months

5. History of epilepsy or a seizure disorder

6. 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)

7. History of kidney and/or liver failure (including transplant)

8. History of head trauma or prior seizure; family history of a seizure disorder, brain
(or central nervous system) tumor

9. Use of pacemakers, certain metallic implants, or presence of metal in the eye as
contraindicated for MRI (magnetic resonance imaging);

10. Low or borderline intellectual functioning - determined by receiving a score <80 on
the Shipley verbal IQ Test

11. Non-English speaking; determined at phone screen

12. History of claustrophobia (contraindicated for MRI) or color blindness (task requires
color recognition); self-report at telephone screen

13. Being left-handed

14. Any fore-limb deformity

15. Wearing cochlear implant or bi-lateral hearing aids

General Exclusion

1. Any medical condition or concomitant medication that could compromise participant
safety or treatment, as determined by the Principal Investigator and/or Study

2. Inability to provide informed consent or complete any of the study tasks as
determined by the Principal Investigator and/or Study Physician.

3. Any physical or visual impairment that may prevent the individual from using a
computer keyboard or completing any study tasks.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Percent Change BOLD Signal

Outcome Description:

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.

Outcome Time Frame:

Day 13

Safety Issue:


Principal Investigator

Caryn Lerman, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pennsylvania


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

August 2008

Related Keywords:

  • Nicotine Dependence
  • Varenicline, Imaging, fMRI
  • Tobacco Use Disorder



Tobacco Use Research CenterPhiladelphia, Pennsylvania  19104