Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking

NCT05665465 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: Pro001109971R01DA054972-01A1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate how certain childhood experiences influences brain function and responses to nicotine exposure in a group of nonsmoking young adults. The investigators assess responses to nicotine exposure by giving participants a small amount of nicotine or placebo, and then asking them to answer questionnaires. The investigational drugs used in this study are a nicotine nasal spray (i.e., Nicotrol) and/or a nasal spray placebo (made of common kitchen ingredients, including a very tiny amount of pepper extract also called capsaicin). The investigators assess brain function through function magnetic resonance imaging (fMRI), which is a noninvasive procedure that uses a magnetic field to take pictures of your brain while you are performing certain tasks. This study will help us to learn more about why some childhood experiences (adverse childhood experiences, or ACEs) contribute to increased risk for smoking and other substance use.

Conditions

Adverse Childhood Experiences; Nicotine Dependence, Cigarettes

Outcome Measures

Primary Outcomes (5)

• Subjective effects of nicotine nasal spray as measured by the Nicotine Effects Questionnaire

  subjective effects will be measured by the Nicotine Effects Questionnaire at the end of each fixed dose session. This scale measure positive reactions, negative reactions, and dizziness on a scale from 0-3 where 0 is none and 3 is intense.

  during fixed dose session, approximately 3 hrs

• Subjective effects of nicotine nasal spray as measured by a visual analog scale

  subjective effects will be measured on a visual analog scale at the end of each fixed dose session. Ratings will be provided on a scale of 0=not at all to 100=an awful lot.

  during fixed dose session, approximately 3 hrs

• Reinforcing effects of nicotine nasal spray

  reinforcing effects will be measured by the number of choices for nicotine spray (range 0-8) during the forced choice session.

  during choice session, approximately 4 hrs

• Percent BOLD signal change in ventral striatum

  Percent blood oxygen level-dependent (BOLD) signal change during anticipation of monetary gain versus baseline during the Reward Guessing Task will be extracted from the bilateral ventral striatum

  baseline, prior to intervention

• Percent BOLD signal change in inferior frontal gyrus

  Percent BOLD signal change during "rare go" versus "no-go" trials during the Go/No-Go Task will be extracted from the right inferior frontal gyrus

  baseline, prior to intervention

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants will be administered 2 nasal sprays with a combined nicotine content of 0mg nicotine, 0.1mL

Drug: Placebo

0.5mg nicotine

EXPERIMENTAL

Participants will be administered 2 nasal sprays with a combined nicotine content of 0.5 mg nicotine, 0.1mL

Drug: Nicotine nasal spray 0.5 mg; Drug: Placebo

1mg nicotine

EXPERIMENTAL

Participants will be administered 2 nasal sprays with a combined nicotine content of 1.0 mg nicotine, 0.1mL

Drug: Nicotine nasal spray 0.5 mg

Interventions

Nicotine nasal spray 0.5 mg DRUG

Participants will be administered nicotine nasal spray and provide subjective reactions

Also known as: Nicotrol

0.5mg nicotine; 1mg nicotine

Placebo DRUG

Participants will be administered placebo nasal spray and provide subjective reactions

0.5mg nicotine; Placebo

Eligibility Criteria

• Age: 18 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• generally healthy
• years of age
• never smoked a full cigarette or used an equivalent amount of other nicotine or tobacco products
• no tobacco exposure in the past 3 years
• expired air CO level ≤ 3 ppm
• corroboration of non-smoking status from 2 collateral reporters
• breath alcohol value = 0.000

You may not qualify if:

• use of illegal drugs as measured by urine drug screen
• reported history of illicit drug use \> 10 times lifetime
• lifetime history of alcohol use disorder
• binge drinking \> 5 times per month over the past 3 months
• history of serious mental illness including bipolar or psychotic disorders
• significant medical or unstable psychiatric disorders
• systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg
• heart rate ≥ 100 bpm
• use of psychoactive medications (e.g., antidepressants, opioid analgesics, etc.) in the past 6 months
• presence of conditions that would make fMRI unsafe (e.g., pacemaker)
• brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder)
• history of serious traumatic brain injury
• claustrophobia
• lack of firm resolve to refrain from cigarette, e-cigarette or other tobacco use in the coming year
• pregnant, trying to become pregnant, or breastfeeding

Sponsors & Collaborators

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

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Tobacco Use Cessation Devices; Nicotine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Maggie Sweitzer, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maggie Sweitzer, PhD

CONTACT

919-668-0094; maggie.sweitzer@duke.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will sample the three doses of nicotine spray in a counter-balanced crossover design.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: December 27, 2022
• Study Start: January 19, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)