Mechanistic Evaluations of Pre-Cessation Therapies for Smoking Cessation (ConNicBrain)

The purpose of this study is to look at brain function in order to understand how different treatments work to help people quit smoking. In this study, the investigators will look at the effects of nicotine patches, Chantix alone or Chantix paired with Zyban.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Drug: Bupropion; Drug: Varenicline; Drug: Nicotine patches; Other: Placebo patch; Other: Placebo bupropion; Other: Placebo varenicline

• Study Type: Interventional
• Enrollment (Actual): 282
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Center for Nicotine and Smoking Cessation Research
    • Raleigh, North Carolina, United States, 27609
      • Duke Center for Nicotine and Smoking Cessation Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Are generally healthy;
• Are 18-50 years old;
• Smoke an average of at least 10 cigarettes per day for at least three cumulative years;
• Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm;
• Are right-handed as measured by a two-item scale used in our laboratory;
• Express a desire to quit smoking in the next thirty days.
• Potential subjects must agree to use acceptable contraception during their participation in this study.

Potential subjects must agree to avoid the following during their participation in this study:

• participation in any other nicotine-related modification strategy outside of this protocol;
• use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco;
• use of experimental (investigational) drugs or devices;
• use of illegal drugs;
• use of opiate medications.

Exclusion Criteria:

• Inability to attend all required experimental sessions;
• Presence of conditions that would make MRI unsafe (e.g. pacemaker);
• Hypertension (systolic >140 mm Hg, diastolic >100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
• Hypotension with symptoms (systolic <90 mm Hg, diastolic <60 mm Hg).
• Coronary heart disease;
• Lifetime history of heart attack;
• Cardiac rhythm disorder (irregular heart rhythm);
• Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
• Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
• History of skin allergy;
• Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
• Liver or kidney disorder (except kidney stones, gallstones);
• Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
• Active ulcers in the past 30 days;
• Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
• Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
• Migraine headaches that occur more frequently than once per week;
• Recent, unexplained fainting spells;
• Problems giving blood samples;
• Diabetes;
• Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
• Other major medical condition;
• Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD));
• Bulimia or anorexia;
• Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
• Current depression;
• Pregnant or nursing mothers;
• Alcohol abuse;
• Significant adverse reaction to nicotine patch, bupropion/Wellbutrin/Zyban or Chantix/Varenicline in the past.

• Use (within the past 30 days) of:

  • Illegal drugs (or if the urine drug screen is positive);
  • Experimental (investigational) drugs;
  • Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
  • Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;
  • Nicotine replacement therapy or any other smoking cessation aid.

• Use (within the past 14 days) of:

  • Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: varenicline; For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline, smokers in this group will also receive placebo bupropion and placebo patches.	Drug: Varenicline; Other Names: Chantix; Drug: Nicotine patches; Other Names: Nicoderm; Other: Placebo patch; Other: Placebo bupropion
Active Comparator: NRT (nicotine patches only); 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.	Drug: Nicotine patches; Other Names: Nicoderm; Other: Placebo bupropion; Other: Placebo varenicline
Active Comparator: varenicline + bupropion; For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week plus bupropion at a dose of 150mg once per day. Subsequently, the dose of varenicline will be 1 mg twice per day and the dose of bupropion will be 150 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline and bupropion, smokers in this group will also receive placebo patches.	Drug: Bupropion; Other Names: Zyban; Drug: Varenicline; Other Names: Chantix; Drug: Nicotine patches; Other Names: Nicoderm; Other: Placebo patch
Placebo Comparator: Post-quit NRT; Nicotine patches at 21 mg/24 h for 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.	Drug: Nicotine patches; Other Names: Nicoderm; Other: Placebo patch; Other: Placebo bupropion; Other: Placebo varenicline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences	Mean blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) cue-reactivity signal following 2 week pre-quit treatment, controlling for baseline cue-reactivity.	change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to First Cigarette Following Quitting Smoking	Days to first cigarette (i.e. lapse) will be measured via self-report.	Up to 11 weeks post quit day.

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: F. Joseph McClernon, Ph.D., Duke University

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: June 12, 2011
• First Submitted That Met QC Criteria: July 28, 2011
• First Posted (Estimate): August 1, 2011

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: fMRI; Smoking cessation; varenicline; bupropion; Nicotine addiction; Cigarette smoking; Zyban; Chantix; Nicotine patches
• 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; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Nicotine; Bupropion; Varenicline
• Other Study ID Numbers: Pro00028331; 1P50DA027840-01A1 (U.S. NIH Grant/Contract)