Measuring Neuroadaptations in Response to Very Low Nicotine Content Cigarettes

Study Overview
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Brief Summary
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The overall goal of this study is to determine if switching to very low nicotine content cigarettes changes the function of brain circuitry involved in incentive salience and executive control among dependent smokers.

Detailed Description
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In a double-blind, randomized controlled trial, dependent smokers will be randomized to a 6-week very low nicotine content (VLNC) cigarette condition (N=50) or a 6-week normal nicotine content cigarette control condition (NNC; N=25). Participants will undergo functional magnetic resonance imaging (fMRI) scans at baseline and 6-weeks to investigate the nicotine-related modulation of brain circuitry involved in incentive salience valuation and executive control. Imaging tasks will engage the incentive salience of smoking cues and non-smoking rewards and executive control functions to identify changes in functional activity within, and effective connectivity between, known salience and executive control brain circuitry. A novel fMRI task using specialized odor presentation equipment and fMRI sequences will assess neural cue reactivity to smoke odors.

Official Title
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Measuring Neuroadaptations in Response to Very Low Nicotine Content Cigarettes

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Drug: Very low nicotine content cigarettes
* Drug: Normal nicotine content cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21-60 years old Smoke >5 cigarettes per day >1 year of daily smoking No quit attempt in prior month and not planning to quit smoking within next 3 months Able to understand and consent to study procedures High school or lower educational attainment or annual household income < $50,000 Plan to live in local area next 3 months Women not pregnant or nursing and taking steps to avoid pregnancy Able to read and write in English Access to computer with internet service that allows for Zoom Exclusion Criteria: Use of non-cigarette tobacco products in the past 7 days Use of illicit substances more than once a week in the past 3 months (excluding marijuana) Current alcohol abuse impairing participation MRI safety contraindications (e.g., metal implants, claustrophobia) Unstable or significant medical conditions (e.g., COPD, coronary heart disease) Major neurological conditions or brain trauma Major surgeries planned in next 3 months Use of smoking cessation medication in prior month (e.g., varenicline, patch) Uncontrolled serious mental illness, suicidality, or inpatient psychiatric hospitalization in the past 6 months Unwillingness to provide urine samples Unwilling to smoke study assigned cigarettes for the remainder of the trial Plans to move or take extended travel out of the area in the next 3 months Any other condition or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol Self-reported color blindness Left-handedness Smell dysfunction as determined via standardized assessment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very low nicotine content cigarettes<br>Research cigarettes with very low nicotine content (0.03 mg/cigarette) compared to usual brand cigarettes. | Drug: Very low nicotine content cigarettes<br>* Very low nicotine content cigarettes<br>|
| Placebo Comparator: Normal nicotine content cigarettes<br>Research cigarettes with normal nicotine content (0.8 mg/cigarette) similar to usual brand cigarettes. | Drug: Normal nicotine content cigarettes<br>* Normal nicotine content cigarettes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood oxygen level dependent (BOLD) activity collected by fMRI | Effect of nicotine content on changes in task-related functional brain activation over 6-weeks | Changes in BOLD from baseline to the 6-week visit. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco, Nicotine, Smoking, Functional magnetic resonance imaging, Addiction