Neuroimaging Reward, Behavioral Treatment, and Smoking Cessation

Study Overview
=================
Brief Summary
-----------------
The goal of this study is to evaluate the effects of a smoking cessation intervention combining behavioral treatment with low nicotine cigarettes on neuroimaging measures of reward function and smoking cessation outcomes. The results of this study will provide information about mechanisms contributing to smoking and smoking cessation and will help to guide future treatment studies.

Detailed Description
-----------------
Smokers who are interested in quitting will be randomly assigned to one of two treatment conditions. In the BA +VLNC condition (n = 16) smokers will switch to smoking very low nicotine cigarettes (VLNCs) while wearing a 21 mg/d nicotine patch for 5 weeks prior to their quit date. They will also participate in weekly behavioral activation (BA) treatment sessions. Smokers in the VLNC Only group (n = 19) will undergo the same pharmacological pretreatment but will undergo standard counseling and health education instead of BA. Following the quit date, both groups will receive standard nicotine replacement therapy. At baseline and pre-quit, BOLD response to smoking and non-smoking rewards will be measured using fMRI after 24 hr abstinence. Latency to relapse will serve as a continuous clinical outcome measure. Participants will also receive follow-up phone calls at 6 months and 12 months post-quit to assess smoking status.

Official Title
-----------------
Targeting Reward Dysfunction as a Mechanism to Improve Smoking Cessation

Conditions
-----------------
Smoking

Intervention / Treatment
-----------------
* Drug: Nicotine Patch
* Drug: SPECTRUM Nicotine Research Cigarettes (.03 mg)
* Behavioral: Behavioral Activation
* Behavioral: Supportive Counseling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: generally healthy intact intellectual functioning (K-BIT2 >79) smoking at least 5 cigarettes per day expired CO concentration of at least 8 ppm or urinary cotinine > 100 ng/mL interested in quitting smoking Exclusion Criteria: inability to attend all experimental sessions report of significant health problems use of psychoactive medications or current participation in psychotherapy current unstable psychiatric illness as assessed by clinical diagnostic interview suicidal ideation with plan or intent regular use of smokeless tobacco current alcohol or drug abuse use of illegal drugs (excluding marijuana) as measured by urine drug screen current use of nicotine replacement therapy or other smoking cessation treatment presence of contraindications for nicotine replacement therapy left-handed presence of conditions that would make MRI unsafe claustrophobia history of fainting pregnant, trying to become pregnant, or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BA + VLNC<br>Participants will receive Nicotine Patch, SPECTRUM Nicotine Research Cigarettes (.03), and behavioral treatment prior to quit attempt, followed by standard nicotine replacement therapy with Nicotine Patch during the quit attempt. Behavioral treatments in this condition will include standard smoking cessation counseling plus behavioral activation therapy aimed at increasing reinforcement from non-drug rewards. | Drug: Nicotine Patch<br>* Both groups will receive nicotine patches (21 mg/d) to wear for 1 month prior to the quit date. After the quit date, both groups will wear the nicotine patch for 8 weeks (21 mg/d for 4 weeks, 14 mg/d for 2 weeks, and 7 mg/d for 2 weeks).<br>* Other names: Nicoderm CQ;Drug: SPECTRUM Nicotine Research Cigarettes (.03 mg)<br>* For 1 month prior to their quit date, participants will switch to smoking SPECTRUM Nicotine Research Cigarettes instead of their usual brand.<br>* Other names: Very Low Nicotine Content Cigarettes;Behavioral: Behavioral Activation<br>* Participants in the BA+VLNC group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of behavioral activation treatment. BA components will include activity monitoring, values assessment, activity scheduling, and social contracts.<br>* Other names: BA;|
| Active Comparator: VLNC Only<br>Participants will receive Nicotine Patch, SPECTRUM Nicotine Research Cigarettes (.03), and behavioral treatment prior to quit attempt, followed by standard nicotine replacement therapy with Nicotine Patch during quit attempt. Behavioral treatments in this condition will include standard smoking cessation counseling plus supportive counseling and health education. | Drug: Nicotine Patch<br>* Both groups will receive nicotine patches (21 mg/d) to wear for 1 month prior to the quit date. After the quit date, both groups will wear the nicotine patch for 8 weeks (21 mg/d for 4 weeks, 14 mg/d for 2 weeks, and 7 mg/d for 2 weeks).<br>* Other names: Nicoderm CQ;Drug: SPECTRUM Nicotine Research Cigarettes (.03 mg)<br>* For 1 month prior to their quit date, participants will switch to smoking SPECTRUM Nicotine Research Cigarettes instead of their usual brand.<br>* Other names: Very Low Nicotine Content Cigarettes;Behavioral: Supportive Counseling<br>* Participants in the VLNC Only group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of supportive counseling and health education. Supportive counseling and health education will include empathic listening as well as informational content on topics of exercise, nutrition, sleep and relaxation.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BOLD (Blood-oxygen-level-dependent) Response to Monetary Reward | Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to monetary reward anticipation. BOLD signal change is estimated from the contrast of monetary reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point. | baseline, week 5 | 
| Change in BOLD (Blood-oxygen-level-dependent) Response to Smoking Reward | Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to smoking reward anticipation. BOLD signal change is estimated from the contrast of smoking reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point. | baseline, week 5 | 
| Number of Participants Who Relapsed or Are Presumed to Have Relapsed | Relapse is defined as return to 7 consecutive days of smoking. | weeks 6 to 13 |