Mechanistic Evaluations of Pre-Cessation Therapies for Smoking Cessation

NCT01406223 | Completed Phase 3 Results DMC

• 2 other identifiers: Pro000283311P50DA027840-01A1
• Study Type: interventional
• Target: 282
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Nicotine Dependence

Keywords

Nicotine addiction; Cigarette smoking; Smoking cessation; Zyban; Chantix; Nicotine patches; varenicline; bupropion; fMRI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Days to First Cigarette Following Quitting Smoking

  Up to 11 weeks post quit day.

Study Arms (4)

varenicline

ACTIVE COMPARATOR

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; Drug: Nicotine patches; Other: Placebo bupropion; Other: Placebo patch

NRT (nicotine patches only)

ACTIVE COMPARATOR

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: Placebo varenicline; Other: Placebo bupropion

varenicline + bupropion

ACTIVE COMPARATOR

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: Varenicline; Drug: Bupropion; Drug: Nicotine patches; Other: Placebo patch

Post-quit NRT

PLACEBO COMPARATOR

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: Placebo varenicline; Other: Placebo bupropion; Other: Placebo patch

Interventions

Varenicline DRUG

Also known as: Chantix

varenicline; varenicline + bupropion

Bupropion DRUG

Also known as: Zyban

varenicline + bupropion

Nicotine patches DRUG

Also known as: Nicoderm

NRT (nicotine patches only); Post-quit NRT; varenicline; varenicline + bupropion

Placebo varenicline OTHER

NRT (nicotine patches only); Post-quit NRT

Placebo bupropion OTHER

NRT (nicotine patches only); Post-quit NRT; varenicline

Placebo patch OTHER

Post-quit NRT; varenicline; varenicline + bupropion

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Duke University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Duke Center for Nicotine and Smoking Cessation Research

Durham, North Carolina, 27705, United States

Location

Duke Center for Nicotine and Smoking Cessation Research

Raleigh, North Carolina, 27609, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Cigarette Smoking; Smoking Cessation

Interventions

Varenicline; Bupropion; Tobacco Use Cessation Devices; Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Tobacco Smoking; Smoking; Behavior; Tobacco Use; Health Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Propiophenones; Ketones; Organic Chemicals; Therapeutics; Solanaceous Alkaloids; Alkaloids; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Statistical comparisons of imaging data between groups are limited due to small sample size in each condition.

Results Point of Contact

• Title: Principal Investigator
• Organization: Duke University Medical Center

francis.mcclernon@duke.edu

919-668-3987

Study Officials

• F. Joseph McClernon, Ph.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2011
• First Posted: August 1, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: November 14, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-10

Locations

US (2)