Clinical trial NCT02514720: Nicotine Metabolizers and [11C]-(+)-PHNO
Official title: Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
First posted: 2015-08-04
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to investigate the effects of nicotine metabolism on occupancy of \[11C\]-(+)-PHNO to DA 2/3 receptors in different brain areas during periods of abstinence and smoking during an abstinence. This will be a Positron Emission Tomography (PET) study and the radiotracer \[11C\]-(+)-PHNO (11C\]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho\[1,2-b\]\[1,4\]oxazin-9-ol) will be used.

Detailed description: The participants will undergo a PET scan after approximately 48 hours abstinence (to ensure total elimination of nicotine in both FMs and SMs) and then approximately \>5 hours later may have a second PET scan after smoking their preferred cigarette (approximately 1 hour before). It is possible that these two scans may also occur on separate days. All subjects will provide a urine sample for (1) drug toxicology, (2) pregnancy test (in females) and (3) Total Nicotine Equivalents (TNE: a measure of total consumption unaltered by rate of nicotine metabolism). There will one blood draw taken before and one after each PET scan (about 20mls in total) to measure nicotine and COT levels (to assess abstinence) as well as kinetics of nicotine delivery. Participants will be given questionnaires prior to, or during, and/or after one or both of the PET scans to determine differences between abstinence and smoking on subjective measures..

Eligibility criteria: Inclusion Criteria:

* Males and females of any ethnic origin 18 years of age or older.
* No previous use of medication for smoking cessation in previous month-
* Non-treatment seeker
* Either SMs or FMs by NMR

Exclusion Criteria:

* DSM-IV diagnosis of other drug dependences
* Any medical condition requiring immediate investigation or treatment
* Pregnancy tested by urine or lactation by self-report
* Current diagnosis of any Axis I psychiatric disorder
* Regular use of any therapeutic or recreational psychoactive drug use that may interfere with PET scanning
* Exposure to radiation in the last 12 months exceding permissible limit for participants participating in research
* Current use of medication that may interfere with \[11C\]-(+)-PHNO
* Metal implants or paramagnetic objects within the body which may interfere with the MRI
* Claustrophobia or a history of panic attacks
* Having any clinical condition, drug sensitivity, or prior therapy which, in the investigator's opinion, makes the participant unsuitable for the study
* Current use of antidepressants that may inhibit CYP2A6 or impact response to nicotine

Primary outcomes:
measure: Occupancy of D2/3 receptors by [11C]-(+)-PHNO
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Bernard Le Foll, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Di Ciano P, Tyndale RF, Mansouri E, Hendershot CS, Wilson AA, Lagzdins D, Houle S, Boileau I, Le Foll B. Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers. Int J Neuropsychopharmacol. 2018 Jun 1;21(6):503-512. doi: 10.1093/ijnp/pyx119.