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

Primary Purpose

Nicotine Dependence

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
cigarette
Sponsored by
Centre for Addiction and Mental Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Nicotine Dependence

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Fast Nicotine Metabolizers

Slow Nicotine Metabolizers

Arm Description

Those in the upper tertile of NMR for cigarette/nicotine metabolism.

Those in the lower tertile of NMR for cigarette/nicotine metabolism

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
July 30, 2015
Last Updated
September 10, 2018
Sponsor
Centre for Addiction and Mental Health
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1. Study Identification

Unique Protocol Identification Number
NCT02514720
Brief Title
Nicotine Metabolizers and [11C]-(+)-PHNO
Acronym
MET
Official Title
Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco Smokers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health

4. Oversight

Data Monitoring Committee
No

5. Study Description

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..

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Dependence

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fast Nicotine Metabolizers
Arm Type
Other
Arm Description
Those in the upper tertile of NMR for cigarette/nicotine metabolism.
Arm Title
Slow Nicotine Metabolizers
Arm Type
Other
Arm Description
Those in the lower tertile of NMR for cigarette/nicotine metabolism
Intervention Type
Other
Intervention Name(s)
cigarette
Intervention Description
Participants will be allowed to smoke a cigarette prior to a PET scan and be abstinent from smoking prior to the other PET scan
Primary Outcome Measure Information:
Title
Occupancy of D2/3 receptors by [11C]-(+)-PHNO
Description
Fast and slow nicotine metabolizers will have PET scans and occupancy of dopamine receptors will be measured using a PET scanner.
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernard Le Foll, MD, PHD
Organizational Affiliation
Centre for Addiction and Mental Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre for Addiction and Mental Health
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5S 1S8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29346545
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.
Results Reference
background
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/29346545
Description
Published data may be found at site above and PMID 29346545

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

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