Clinical trial NCT00602927: Effects of Varenicline on Brain Activity During Nicotine Abstinence
Official title: Neural Substrates of Varenicline's (Chantix®) Efficacy for Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Keywords: Varenicline, Imaging, fMRI
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Pfizer
name: National Cancer Institute (NCI)
First posted: 2008-01-28
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This project aims to define mechanisms through which varenicline might be an effective smoking cessation medication.

Detailed description: 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.

Eligibility criteria: 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 months
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 medications:

   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 Physician.
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.

Primary outcomes:
measure: Percent Change BOLD Signal
timeFrame: Day 13
Secondary outcomes:
measure: Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time)
timeFrame: Day 13
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Tobacco Use Research Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Caryn Lerman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loughead J, Ray R, Wileyto EP, Ruparel K, Sanborn P, Siegel S, Gur RC, Lerman C. Effects of the alpha4beta2 partial agonist varenicline on brain activity and working memory in abstinent smokers. Biol Psychiatry. 2010 Apr 15;67(8):715-21. doi: 10.1016/j.biopsych.2010.01.016. Epub 2010 Mar 6.