Effects of Varenicline on Brain Activity During Nicotine Abstinence

NCT ID: NCT00602927

Last Updated: 2011-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2008-08-31

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.

Conditions

Nicotine Dependence

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will take placebo pills for 13 days using the same regimen as the varenicline study period.

Varenicline

Group Type: ACTIVE_COMPARATOR

Varenicline

Intervention Type: DRUG

Day 1 - Day 3 0.5mg once daily Day 4 - Day 7 0.5mg twice daily Day 8 - Day 13 1.0mg twice daily

Interventions

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

Intervention Type: DRUG

Placebo

Participants will take placebo pills for 13 days using the same regimen as the varenicline study period.

Intervention Type: DRUG

Other Intervention Names

Chantix

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

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

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

University of Pennsylvania

Principal Investigators

Caryn Lerman, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Tobacco Use Research Center

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 20207347 (View on PubMed)

Other Identifiers

GA30517A

Identifier Type: OTHER

Identifier Source: secondary_id

P50CA084718

Identifier Type: NIH

Identifier Source: secondary_id

View Link

806623

Identifier Type: -

Identifier Source: org_study_id