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

Duke University

Status and phase: Completed; Phase 3

Conditions: Nicotine Dependence

Treatments: Other: Placebo varenicline; Drug: Varenicline; Other: Placebo patch; Drug: Bupropion; Drug: Nicotine patches; Other: Placebo bupropion

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01406223

Pro00028331

1P50DA027840-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 282 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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282 participants in 4 patient groups, including a placebo group

varenicline

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Nicotine patches

Other: Placebo bupropion

Drug: Varenicline

NRT (nicotine patches only)

Active Comparator group

Description:

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.

Treatment:

Drug: Nicotine patches

Other: Placebo bupropion

Other: Placebo varenicline

varenicline + bupropion

Active Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Nicotine patches

Drug: Bupropion

Drug: Varenicline

Post-quit NRT

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo patch

Drug: Nicotine patches

Other: Placebo bupropion

Other: Placebo varenicline