Measuring Neuroadaptations in Response to Very Low Nicotine Content Cigarettes

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Dependence
• Intervention / Treatment: Drug: Very low nicotine content cigarettes; Drug: Normal nicotine content cigarettes

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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., chronic obstructive pulmonary disorder, 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task	Change from baseline to 6-weeks post-intervention in percentage of BOLD signal during hard vs. no choice conditions on a monetary delay discounting task in a left-sided cortical brain region encompassing the central opercular and dorsolateral prefrontal cortices.	Change in BOLD signal from baseline to the 6-week visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Self-reported Cigarettes Per Day	Difference in week 6 mean minus week 1 mean of cigarettes used per day reported by participants on daily logs.	Average cigarettes per day during week 1 subtracted from average cigarettes per day during week 6.
Change in Percentage of Immediate Choices on Monetary Delay Discounting Task	A difference score (6-weeks minus baseline) of the percentage of trials where the immediate (vs. delayed) monetary option was chosen out of all task trials during the monetary delay discounting task that was completed outside of the MRI scan.	Changes from baseline to 6-weeks post intervention.

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Andrea Hobkirk, PhD, Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Smoking; Tobacco; Addiction; Functional magnetic resonance imaging; Nicotine
• 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; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 9276; K23DA045081 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No