Brain Imaging in Tobacco Smokers During a Quit Attempt

NCT04055467 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB001735361R21DA047795-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study will help fill gaps in existing research by determining if nicotine-dependent cigarette smokers show changes in α7 nicotinic acetylcholine receptor (nAChR) availability when compared to matched historical controls using positron emission tomography (PET) imaging and the radioactive ligand \[18F\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide), an α7 nAChR antagonist. The study will also explore whether α7 nAChR availability influences clinically relevant measures of tobacco abstinence (e.g., withdrawal and craving, cognitive impairment), self-reported cigarettes per day, and time to relapse during an 8-day quit attempt during which smokers can receive escalating payments contingent upon providing objective evidence (breath CO and urinary cotinine) of smoking abstinence.

Conditions

Tobacco Use Disorder; Tobacco Smoking

Keywords

smoking cessation; neuroimaging; nicotinic acetylcholine receptors; abstinence

Outcome Measures

Primary Outcomes (3)

• Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan

  Distribution volume (VT) in volumes of interest (VOI) in tobacco smokers. VOI are cingulate, hippocampus, frontal cortex, amygdala, and ventral striatum. VOI are defined via each individual subject's Magnetic Resonance Imaging for anatomical identification of the VOI for alignment with PET images.

  1 day

• Total Withdrawal Score on the Minnesota Nicotine Withdrawal Scale (MNWS) on Day of PET Scan

  Self-report form has a 15-item list of symptoms where subjects self-rate symptom severity on a scale of 0-4. Validated symptoms for tobacco withdrawal in smokers will be used for the study to quantify total withdrawal symptoms at baseline (smoking as usual), when compared to symptoms on the day of the PET scan. Scores for each item range from 0-4, with 0 representing no symptoms and 4 representing severe withdrawal symptoms. The score range for validated symptoms is 0-36. Higher scores indicate greater nicotine withdrawal severity. Results reported are scores from day of PET scan.

  1 day

• Craving/Urge to Smoke as Determined Via the Questionnaire of Subjective Urges (QSU) on Day of PET Scan

  The QSU is a 10-item questionnaire to measure craving/urges to smoke. For each item, subjects rate how strongly the subject feel "right now" on a Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Items are summed to yield two factor scores, Factor 1 Intention/desire to smoke (minimum score=5, maximum score=35), and Factor 2: Relief of negative affect and Urgent desire to smoke (minimum score=5, maximum score=35). Factor 1 and Factor 2 scores are combined, with a score range of 10-70, higher score indicating maximum cravings/urges to smoke (worse). Results reported reflect QSU scores on day of PET scan vs baseline.

  1 day

Secondary Outcomes (5)

• Cigarettes Smoked Per Day

  3 months

• Number of Days of Smoking Abstinence on Day of PET Scan

  1 day

• Negative Mood as Determined by the Positive and Negative Affect Scale (PANAS)

  Baseline, Day of PET

• Attention as Assessed by Connors Continuous Performance Task

  Baseline, Day of PET

• Performance on the Paced Serial Addition Task (PASAT)

  Baseline, Day of PET

Study Arms (1)

[F18]-ASEM + Contingency Management

OTHER

PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments.

Drug: [F18]-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[18F]fluorodibenzo[b,d]thiophene 5,5-dioxide); Behavioral: Contingency Management

Interventions

[F18]-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[18F]fluorodibenzo[b,d]thiophene 5,5-dioxide) DRUG

Brain imaging of alpha-7 nicotinic acetylcholine receptors

Also known as: [F18]-ASEM

[F18]-ASEM + Contingency Management

Contingency Management BEHAVIORAL

Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits

Also known as: Incentive payments

[F18]-ASEM + Contingency Management

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be healthy volunteers
• Regular tobacco smokers for a period of 2 or more years
• Positive breath carbon monoxide (CO)
• Cotinine positive urine test
• Meet DSM-V criteria for tobacco use disorder.

You may not qualify if:

• Meets DSM-5 criteria for alcohol use disorder or substance use disorder (excluding tobacco use disorder)
• Meets DSM-5 Psychiatric Disorder; in or in need of treatment
• History of seizures, seizure disorder or closed head trauma
• HIV positive
• Weight \> 350 lbs
• \< 5th grade reading level
• Recent use of smoking cessation products
• If female: pregnant, lactating, planning pregnancy; positive urine pregnancy screen
• Any condition which would preclude MRI
• Radiation exposure in the last year that when combined with the study protocol would exceed the annual limits.

Sponsors & Collaborators

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

Study Sites (1)

Elise Weerts

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Tobacco Smoking; Smoking Cessation

Interventions

3-(1,4-diazabicyclo(3.2.2)nonan-4-yl)-6-fluorodibenzo(b,d)thiophene 5,5-dioxide

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior; Tobacco Use; Health Behavior

Results Point of Contact

• Title: Dr. Elise Weerts, Professor
• Organization: Johns Hopkins School of Medicine

eweerts@jhmi.edu

410-550-2781

Study Officials

• Elise Weerts, Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2019
• First Posted: August 13, 2019
• Study Start: December 16, 2019
• Primary Completion: October 30, 2022
• Study Completion: November 30, 2022
• Last Updated: August 6, 2024
• Results First Posted: August 6, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)