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Effects of Varenicline on Brain Activity During Nicotine Abstinence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00602927
Recruitment Status : Completed
First Posted : January 28, 2008
Results First Posted : May 2, 2011
Last Update Posted : May 10, 2011
National Cancer Institute (NCI)
Information provided by:
University of Pennsylvania

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

Condition or disease Intervention/treatment Phase
Nicotine Dependence Drug: Varenicline Drug: Placebo Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Neural Substrates of Varenicline's (Chantix®) Efficacy for Smoking Cessation
Study Start Date : November 2007
Actual Primary Completion Date : August 2008
Actual Study Completion Date : August 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo Drug: Placebo
Participants will take placebo pills for 13 days using the same regimen as the varenicline study period.

Active Comparator: Varenicline Drug: Varenicline
Day 1 - Day 3 0.5mg once daily Day 4 - Day 7 0.5mg twice daily Day 8 - Day 13 1.0mg twice daily
Other Name: Chantix

Primary Outcome Measures :
  1. Percent Change BOLD Signal [ Time Frame: Day 13 ]
    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.

Secondary Outcome Measures :
  1. Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) [ Time Frame: Day 13 ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00602927

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United States, Pennsylvania
Tobacco Use Research Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
National Cancer Institute (NCI)
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Principal Investigator: Caryn Lerman, PhD University of Pennsylvania

Publications of Results:
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Responsible Party: Dr. Caryn Lerman, University of Pennsylvania Identifier: NCT00602927     History of Changes
Other Study ID Numbers: 806623
GA30517A ( Other Identifier: Pfizer )
P50CA084718 ( U.S. NIH Grant/Contract )
First Posted: January 28, 2008    Key Record Dates
Results First Posted: May 2, 2011
Last Update Posted: May 10, 2011
Last Verified: May 2011

Keywords provided by University of Pennsylvania:
Varenicline, Imaging, fMRI

Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs