Brain Imaging in Tobacco Smokers During a Quit Attempt
Condition: Tobacco Use Disorder; Tobacco Smoking
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): [F18]-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-[18F]fluorodibenzo[b,d]thiophene 5,5-dioxide); Contingency Management
Intervention type(s): Drug; Behavioral
Intervention description(s): Brain imaging of alpha-7 nicotinic acetylcholine receptors; Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Other intervention name(s): [F18]-ASEM; Incentive payments
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: smoking cessation; neuroimaging; nicotinic acetylcholine receptors; abstinence