Effects of Varenicline on Smoking Reminders (VSMK)

Characterizing a Cue-vulnerable Pharmaco-responsive Endophenotype in Smokers

Varenicline is the best smoking cessation agent to date; however it is only effective in a subgroup of smokers and is associated with undesirable side effects in other subgroups. To understand the underlying pharmaco-heterogeneity, the proposed project will use perfusion functional magnetic resonance imaging and a functional candidate gene association approach using brain, behavioral, and clinical endpoints in a placebo-controlled study of chronic varenicline administration in smokers. Brain and behavioral responses to smoking cues will be will be significantly greater in 9/10-repeats compared to 10/10-repeats. DAT 9/10-repeat smokers receiving varenicline will have better treatment outcome compared to 10/10-repeats. For the purposes of the clinical trial portion of the study, the change from cigarettes per day at Baseline to the last day of treatment will be reported.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Placebo; Drug: Varenicline

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Addiction Treatment Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Physically healthy male or female nicotine dependent patients ages 18-60 without other current drug dependence or psychiatric diagnosis.
• Smoke ≥ 10 cigarettes per day for at least 6 months prior to study start date.
• Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of child bearing potential but practicing a medically acceptable method of birth control from at least 2 weeks prior to screening until 30 days after the last dose of varenicline. Examples of medically acceptable methods for this protocol include barrier (diaphragm or condom) with spermicide, an intrauterine (IUD), oral contraceptives, levonorgestrel implant, or complete abstinence.
• Subjects provide voluntary informed consent.
• Subjects must read at 8th grade level or higher.

Exclusion Criteria:

• History of head trauma or injury causing loss of consciousness, lasting more than three (3) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
• Presence of magnetically active prosthetics, plates, pins, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
• Self report of HIV positive and on medication for symptoms: Determined on an individual basis by results from the physical examination and final approval by the study physician.
• Symptomatic presence of other hematological disease.
• Clinically significant hepatic (liver), renal (kidney), neurological, or endocrinological abnormalities.
• History of any cardiovascular event within the last 6 months and any serious/significant cardiovascular event in the subject's life. This will be determined on an individual basis by the study physician.
• History of psychosis or seizures.
• Use of medications or natural herbs that may cause sedation or may effect the brain systems that are being studied (medication use will be evaluated on a case-by-case basis).
• Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.	Drug: Placebo; Placebo will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective for Varenicline: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.; Other Names: Sugar Pill
Active Comparator: Varenicline; Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.	Drug: Varenicline; Varenicline will be prescribed to non-abstinent smokers at the same doses as have been demonstrated to be clinically effective: 0.5 mg twice a day for 3 days and then 1mg twice daily for the remainder of the treatment course of 8 weeks.; Other Names: Chantix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cigarettes Per Day	Cigarettes per day at Baseline versus 8 weeks of treatment, placebo-controlled	last week of treatment (1-8 weeks)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Teresa Franklin, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 10, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 2, 2012

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: fMRI; varenicline; Smokers
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 813779; 1R01DA029845-01A1 (U.S. NIH Grant/Contract)