Adverse Childhood ExperiencesEarly Phase 1NCT05665465
Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking
A Early Phase 1 study testing Nicotine nasal spray 0.5 mg in people with Adverse Childhood Experiences and Nicotine Dependence, Cigarettes, run by Duke University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Adverse Childhood Experiences, Nicotine Dependence, Cigarettes
- What is being tested?
- Nicotine nasal spray 0.5 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jan 2024to 31 May 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 21 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- generally healthy
- 18-21 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
Who cannot join
- 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
Show all 17Show fewer
- 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
- inability to understand written and/or spoken English language
- inability to attend all experimental sessions
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Maggie Sweitzer, PhD, 919-668-0094, maggie.sweitzer@duke.edu
About this study
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.
Read the detailed description
Individuals with a history of adverse childhood experiences (ACEs) are more likely to smoke cigarettes than those without, but little is known about the factors that account for this increased risk. This study will examine brain function in regions related to reward processing and inhibitory control, along with reactions to initial nicotine exposure to help explain why ACEs lead to increased risk for smoking. In this study, young adult non-smokers ages 18-21 (n=150) with a history of exposure to ACEs ranging from 0 to 4 or more will be enrolled to attend 7 visits including an MRI scan and administration of a nicotine nasal spray. Participants will complete an in-person screening visit, followed by a training visit to provide training for the MRI tasks and to acclimate them to the mock MRI scanner. They will then complete a functional neuroimaging scanning session to examine brain reactivity during a monetary reward task, an inhibitory control task, and during rest. Participants will then attend 3 separate visits in which subjective reactions to a nasal spray containing 0, .5, or 1 mg doses of nicotine will be measured. During a final choice session participants will choose to self-administer nicotine or placebo nasal spray. Breath and urine samples will be collected at each visit to test for recent smoking, alcohol use, or illicit drug use. Plasma samples will be collected at each fixed-dose session to assess nicotine and cotinine levels. All nicotine administration will occur during laboratory sessions, and the study physician will be on site or on call during all visits.
- Being tested
- Nicotine nasal spray 0.5 mg, Placebo
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine nasal spray 0.5 mgDrug
Also called Nicotrol
Participants will be administered nicotine nasal spray and provide subjective reactions
PlaceboDrug
Participants will be administered placebo nasal spray and provide subjective reactions
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will be administered 2 nasal sprays with a combined nicotine content of 0mg nicotine, 0.1mL Receives: 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 Receives: 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 Receives: Drug: Nicotine nasal spray 0.5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: baseline, prior to intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2022
- Study start19 Jan 2024
- Primary completion31 May 2027 (estimated)
- Study completion31 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adverse Childhood ExperiencesStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- All participants will sample the three doses of nicotine spray in a counter-balanced crossover design.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Maggie Sweitzer, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05665465
- Sponsor's protocol ID
- Pro00110997
- Other IDs
- 1R01DA054972-01A1
- Status last verified
- Apr 2026
- First submitted
- 12 Dec 2022
- Last updated
- 2 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking
- ClinicalTrials.gov ID
- NCT05665465
- Acronym / sponsor ID
- Pro00110997
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 19 Jan 2024 (actual)
- Primary completion
- 31 May 2027 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 27 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Individuals with a history of adverse childhood experiences (ACEs) are more likely to smoke cigarettes than those without, but little is known about the factors that account for this increased risk. This study will examine brain function in regions related to reward processing and inhibitory control, along with reactions to initial nicotine exposure to help explain why ACEs lead to increased risk for smoking. In this study, young adult non-smokers ages 18-21 (n=150) with a history of exposure to ACEs ranging from 0 to 4 or more will be enrolled to attend 7 visits including an MRI scan and administration of a nicotine nasal spray. Participants will complete an in-person screening visit, followed by a training visit to provide training for the MRI tasks and to acclimate them to the mock MRI scanner. They will then complete a functional neuroimaging scanning session to examine brain reactivity during a monetary reward task, an inhibitory control task, and during rest. Participants will then attend 3 separate visits in which subjective reactions to a nasal spray containing 0, .5, or 1 mg doses of nicotine will be measured. During a final choice session participants will choose to self-administer nicotine or placebo nasal spray. Breath and urine samples will be collected at each visit to test for recent smoking, alcohol use, or illicit drug use. Plasma samples will be collected at each fixed-dose session to assess nicotine and cotinine levels. All nicotine administration will occur during laboratory sessions, and the study physician will be on site or on call during all visits.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- All participants will sample the three doses of nicotine spray in a counter-balanced crossover design.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will be administered 2 nasal sprays with a combined nicotine content of 0mg nicotine, 0.1mL |
| 0.5mg nicotine | Experimental | Drug: Nicotine nasal spray 0.5 mg, Drug: PlaceboParticipants will be administered 2 nasal sprays with a combined nicotine content of 0.5 mg nicotine, 0.1mL |
| 1mg nicotine | Experimental | Drug: Nicotine nasal spray 0.5 mgParticipants will be administered 2 nasal sprays with a combined nicotine content of 1.0 mg nicotine, 0.1mL |
Who may qualify
- Ages
- 18 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- generally healthy
- 18-21 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotine nasal spray 0.5 mgAlso: NicotrolParticipants will be administered nicotine nasal spray and provide subjective reactions | Drug | 0.5mg nicotine, 1mg nicotine |
| PlaceboParticipants will be administered placebo nasal spray and provide subjective reactions | Drug | 0.5mg nicotine, Placebo |
Primary outcome
Subjective effects of nicotine nasal spray as measured by the Nicotine Effects Questionnaire
Time frame: during fixed dose session, approximately 3 hrs
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.
Subjective effects of nicotine nasal spray as measured by a visual analog scale
Time frame: during fixed dose session, approximately 3 hrs
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.
Reinforcing effects of nicotine nasal spray
Time frame: during choice session, approximately 4 hrs
reinforcing effects will be measured by the number of choices for nicotine spray (range 0-8) during the forced choice session.
Percent BOLD signal change in ventral striatum
Time frame: baseline, prior to intervention
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
Percent BOLD signal change in inferior frontal gyrus
Time frame: baseline, prior to intervention
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Individual participant dataSharing planned: No
Related trials for Adverse Childhood Experiences
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Recruiting
A Pilot Study to Examine the Efficacy of Internet-Delivered Skills Training in Affective and Interpersonal Regulation (i-STAIR) for Individuals With Adverse Childhood Experiences and Subsyndromal Depression
Subthreshold Depression
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Resilient Students Training (ReST) : A Pilot RCT
Psychological Wellness
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EMI for Reducing Psychological Distress in Young Adults With Multiple ACEs: A RCT Study
Psychological Distress, Adverse Childhood Experience
Not yet recruiting
EMI for Reducing Psychological Distress in Young Adults With Multiple ACEs: A Feasibility Study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Maggie Sweitzer, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nicotine nasal spray 0.5 mg in people with Adverse Childhood Experiences and Nicotine Dependence, Cigarettes, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maggie Sweitzer, PhD (919-668-0094, maggie.sweitzer@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Subjective effects of nicotine nasal spray as measured by the Nicotine Effects Questionnaire (time frame: during fixed dose session, approximately 3 hrs). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.