Effects of Varenicline on Brain Activity During Nicotine Abstinence

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00602927
First received: January 15, 2008
Last updated: May 6, 2011
Last verified: May 2011
  Purpose

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


Condition Intervention
Nicotine Dependence
Drug: Varenicline
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Neural Substrates of Varenicline's (Chantix®) Efficacy for Smoking Cessation

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Percent Change BOLD Signal [ Time Frame: Day 13 ] [ Designated as safety issue: No ]
    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:
  • Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) [ Time Frame: Day 13 ] [ Designated as safety issue: No ]
    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.


Enrollment: 38
Study Start Date: November 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602927

Locations
United States, Pennsylvania
Tobacco Use Research Center
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Pfizer
Investigators
Principal Investigator: Caryn Lerman, PhD University of Pennsylvania
  More Information

Publications:
Responsible Party: Dr. Caryn Lerman, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00602927     History of Changes
Other Study ID Numbers: 806623, GA30517A, P50CA084718
Study First Received: January 15, 2008
Results First Received: October 6, 2010
Last Updated: May 6, 2011
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014