Nicotine Metabolizers and [11C]-(+)-PHNO

Nicotine Dependence Clinical Trial

— MET  

Official title:

Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02514720
• Other study ID #: 111/2014
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: January 2017

Study information

• Verified date: June 2017
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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..

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Other:
• cigarette
Participants will be allowed to smoke a cigarette prior to a PET scan and be abstinent from smoking prior to the other PET scan

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occupancy of D2/3 receptors by [11C]-(+)-PHNO	Fast and slow nicotine metabolizers will have PET scans and occupancy of dopamine receptors will be measured using a PET scanner.	2 weeks

External Links

•   Published data may be found at site above and PMID 29346545