Brain Imaging in Tobacco Smokers During a Quit Attempt

Brain Imaging of Nicotinic Acetylcholine Receptors in Tobacco Users and Nonusers

Sponsors

Lead Sponsor: Johns Hopkins University

Collaborator: National Institute on Drug Abuse (NIDA)

Source Johns Hopkins University
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.

Detailed Description

The primary objective of this basic clinical research study is to examine the role of the alpha7-nicotinic acetylcholine receptors (nAChRs) in tobacco use disorder. nAChRs are the primary site of action for nicotine (the main psychoactive component of tobacco). The most common types of nAChRs are heteromeric nAChRs containing beta2 subunits and homomeric nAChRs, which contain only alpha7 subunits. It is currently unknown if or how chronic tobacco use affects alpha7 nAChR in humans. The investigators' working hypothesis is brain alpha7 nAChR density associated with chronic nicotine exposure and the development of tobacco use disorder may be influence severity of tobacco craving and withdrawal during early smoking abstinence.

Proposed group sample sizes are 18 tobacco smokers (accrual) and 18 nonsmokers (drawn from historical and contemporary controls in ongoing studies). Media-recruited male and female heavy smokers will be assessed for study inclusion/exclusion criteria using a structured diagnostic interview and a standard battery of instruments, as well as a medical exam to determine general health. Study candidates also provide breath and urine samples to determine biomarkers of tobacco use (breath carbon oxide and urinary cotinine levels), other drug use (breath alcohol and urine toxicology) and for females a pregnancy test. To ensure there are a sufficient number of subjects, 60 subjects will be screened for study eligibility and assessed for matching criteria (age, race and sex). Groups (smokers vs. non-smokers) will include equal numbers of males and females. In addition, male and female smokers will be matched for tobacco use disorder severity using symptom counts (DSM 5).

Eligible subjects will be enrolled in an outpatient protocol completed at the Behavioral Pharmacology Research Unit (BPRU) at the Johns Hopkins Bayview Medical Center, and at the Johns Hopkins Hospital (JHH) PET imaging Center. Abstinent smokers (as verified by CO and cotinine, see below) will complete an magnetic resonance imaging (MRI) scan and a PET scan with the alpha-7 nAChR radiotracer [18F]-ASEM. Matched historical controls will have completed the MRI and PET scans previously.

Tobacco users will receive contingency management incentive payments for verified smoking abstinence (Intervention 2, behavioral counseling). Smokers will continue in the study after the PET scan and complete an 8-day practice quit attempt. To evaluate smoking abstinence and lapse behavior, smokers will be asked to complete study six visits with a practice quit attempt. Smoker will receive the incentive intervention for smoking abstinence. At each visit, smokers will provide carbon monoxide (CO) and urine samples, and complete assessment instruments to self-report on daily symptoms of nicotine withdrawal and craving, and number of cigarettes smoked. The incentive intervention is a validated, established intervention for smoking cessation. At each visit, smokers will receive escalating incentive payments contingent upon provision of samples that meet study defined abstinence criteria. The incentive earning schedule starts at $9 on day 1 of abstinence and increases by $1.50 for each day of verified abstinence to $19.50 on day 8. To boost the incentive for abstinence, provision of samples that meet bonus abstinence (cotinine <100 ng/ml day 8) results additional $10 or $20 bonus payments. The incentive earnings schedule includes allowance for a slip, and a reset contingency to allow smokers to retry the quit attempt and complete the study. This incentive earnings schedule with resets is of high magnitude to reinforce abstinence, and increase participant retainment. The number of days in the quit attempt (8) yields a sufficient sample to examine both withdrawal and biomarkers (CO and cotinine) to quantify number of days in which use of any nicotine occurred vs. days participants were compliant in maintaining abstinence. These data will be utilized to explore the relationship of alpha7-nAChR availability to these clinically meaningful measures of tobacco use and abstinence.

Overall Status Recruiting
Start Date December 16, 2019
Completion Date June 2021
Primary Completion Date June 2021
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Distribution volume (VT) as determined by [18F]-ASEM PET scan 1 day
Total withdrawal score on the Minnesota Nicotine Withdrawal Scale (MNWS) 2 weeks
Craving/Urge to smoke as determined via the Questionnaire of Subjective Urges (QSU) 2 weeks
Secondary Outcome
Measure Time Frame
Number of Cigarettes smoked per day 3 months
Number of days of smoking abstinence 2 weeks
Negative mood as determined by the Positive and negative affect scale (PANAS) 2 weeks
Attention as assessed by Connors continuous performance task 2 weeks
Performance on the Paced Serial Addition Task (PASAT) 2 weeks
Enrollment 18
Condition
Intervention

Intervention Type: Drug

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

Description: Brain imaging of alpha-7 nicotinic acetylcholine receptors

Arm Group Label: [F18]-ASEM + Contingency Management

Other Name: [F18]-ASEM

Intervention Type: Behavioral

Intervention Name: Contingency Management

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

Arm Group Label: [F18]-ASEM + Contingency Management

Other Name: Incentive payments

Eligibility

Criteria:

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

Gender: All

Minimum Age: 21 Years

Maximum Age: 50 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Elise Weerts, Ph.D. Principal Investigator Johns Hopkins University
Overall Contact

Last Name: Tyrone Scales

Phone: 410-550-1929

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: Johns Hopkins Behavioral Pharmacology Research Unit Tyrone Scales 410-550-1929 [email protected] Elise Weerts, PhD Principal Investigator
Location Countries

United States

Verification Date

March 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: [F18]-ASEM + Contingency Management

Type: Other

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

Patient Data No
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov