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The Effect of Varenicline on D2/D3 Receptor Binding in Smokers

Primary Purpose

Nicotine Dependence

Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Varenicline
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 focused on measuring Varenicline, PET imaging, [11C]-(+)-PHNO PET, neuroimaging in smokers

Eligibility Criteria

21 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects will be nicotine dependent, males and females of any ethnic origin between 21 and 45 years old.
  • Meet DSM-IV criteria for nicotine dependence,
  • Smoke ≥10 cigarettes/day, Baseline FTND score ≥4, CO level ≥10 and are motivated to quit within 30 days of initial intake.
  • Treatment seeking smokers that are willing to use varenicline as a treatment approach for their smoking cessation attempt
  • No previous use of medication for smoking cessation in previous month prior inclusion.

Exclusion Criteria:

  • Pregnancy (a urine pregnancy test will be performed before each PET in women)
  • Trying to become pregnant or breastfeeding;
  • Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 3 months prior to randomization.
  • Presence of metal objects in the body (e.g. some artificial joints, bone pins, surgical clips, skull plate, certain part of dental braces) or implanted electronic devices (e.g. cardiac pacemaker, neurostimulator), that preclude safe MR scanning.
  • Claustrophobia.
  • Cardiovascular or cerebrovascular diseases.
  • Major psychiatric disorders including mood, anxiety or psychotic disorders with historical evidence of suicidal or homicidal behaviour.
  • History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor. Gross structural brain abnormalities as revealed by T1 weighted images.
  • Current use or use during the previous month of medication that may affect the CNS at the time of scanning (including illicit and non-illicit psychoactive drugs).
  • Learning disability, amnesia or other conditions that impede memory and attention.
  • Allergy to varenicline.
  • Renal insufficiency.
  • Use of other smoking cessation aids

Sites / Locations

  • Centre for Addiction and Mental Health

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Varenicline

Arm Description

Varenicline will be used at the same dosage regimen as used for smoking cessation, i.e. 0.5mg once daily for days 1-3, 0.5mg twice daily for days 4-7 followed by 1mg twice daily. The total duration of Varenicline treatment will be three months.

Outcomes

Primary Outcome Measures

[11C]-(+)-PHNO DRD2/3 binding potential (BPND)
The effects of chronic administration of varenicline (standard dose run up protocol to 2 mg per day for 10 days) vs. baseline on [11C]-(+)-PHNO binding in human brain of tobacco smokers (12 hours abstinent).

Secondary Outcome Measures

Relationship between ability to quit smoking and changes in DRD2/3
Relationship between clinical ratings of abstinence and cravings and DRD2/3 normalization after 10-day course of varenicline administration.

Full Information

First Posted
June 28, 2012
Last Updated
January 26, 2016
Sponsor
Centre for Addiction and Mental Health
Collaborators
Ontario Lung Association, Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01632189
Brief Title
The Effect of Varenicline on D2/D3 Receptor Binding in Smokers
Official Title
Investigating the Effects of Varenicline on D2/3 Receptor Binding in Brain of Tobacco-smokers: a PET/[11C](+)PHNO Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centre for Addiction and Mental Health
Collaborators
Ontario Lung Association, Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will evaluate effects of treatment with varenicline, a smoking cessation drug, on the dopaminergic system by using Positron Emission Tomography (PET) imaging with new radioligand, [11C]-(+)-PHNO. The investigators primary hypothesis is that chronic varenicline administration will increase dopamine (DA) receptors levels ([11C](+)PHNO) within the human brain.
Detailed Description
Subjects will undergo a pre-treatment PET and MRI scans for baseline [11C](+)PHNO measures on Day 1. Subjects will subsequently be provided an initial 2-week supply of study medications (varenicline) and directions for use. Any adverse events, compliance to medication and smoking patterns will be noted during these two weeks. Varenicline will be used at the same dosage regimen as used for smoking cessation. After subjects go through a post-treatment PET and MRI scans on Day 10, they will be instructed to set up a quit date. There will then be follow-up visits every 2 weeks for the duration of the medication phase (3 months total) and a visit at 6 months follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Dependence
Keywords
Varenicline, PET imaging, [11C]-(+)-PHNO PET, neuroimaging in smokers

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Varenicline
Arm Type
Experimental
Arm Description
Varenicline will be used at the same dosage regimen as used for smoking cessation, i.e. 0.5mg once daily for days 1-3, 0.5mg twice daily for days 4-7 followed by 1mg twice daily. The total duration of Varenicline treatment will be three months.
Intervention Type
Drug
Intervention Name(s)
Varenicline
Other Intervention Name(s)
Champix
Intervention Description
Varenicline will be administered as prescribed: 0.5 mg for the first 3 days then 1 mg for the next 7 days and 2 mg after that. A quit date will be chosen at 11 days after starting Varenicline. Varenicline will be given for 3 months.
Primary Outcome Measure Information:
Title
[11C]-(+)-PHNO DRD2/3 binding potential (BPND)
Description
The effects of chronic administration of varenicline (standard dose run up protocol to 2 mg per day for 10 days) vs. baseline on [11C]-(+)-PHNO binding in human brain of tobacco smokers (12 hours abstinent).
Time Frame
10 days
Secondary Outcome Measure Information:
Title
Relationship between ability to quit smoking and changes in DRD2/3
Description
Relationship between clinical ratings of abstinence and cravings and DRD2/3 normalization after 10-day course of varenicline administration.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects will be nicotine dependent, males and females of any ethnic origin between 21 and 45 years old. Meet DSM-IV criteria for nicotine dependence, Smoke ≥10 cigarettes/day, Baseline FTND score ≥4, CO level ≥10 and are motivated to quit within 30 days of initial intake. Treatment seeking smokers that are willing to use varenicline as a treatment approach for their smoking cessation attempt No previous use of medication for smoking cessation in previous month prior inclusion. Exclusion Criteria: Pregnancy (a urine pregnancy test will be performed before each PET in women) Trying to become pregnant or breastfeeding; Have abused alcohol or other drugs of abuse (cocaine, opiates, benzodiazepines, etc) in 3 months prior to randomization. Presence of metal objects in the body (e.g. some artificial joints, bone pins, surgical clips, skull plate, certain part of dental braces) or implanted electronic devices (e.g. cardiac pacemaker, neurostimulator), that preclude safe MR scanning. Claustrophobia. Cardiovascular or cerebrovascular diseases. Major psychiatric disorders including mood, anxiety or psychotic disorders with historical evidence of suicidal or homicidal behaviour. History of or current neurological illnesses including seizure disorders, migraine, multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor. Gross structural brain abnormalities as revealed by T1 weighted images. Current use or use during the previous month of medication that may affect the CNS at the time of scanning (including illicit and non-illicit psychoactive drugs). Learning disability, amnesia or other conditions that impede memory and attention. Allergy to varenicline. Renal insufficiency. Use of other smoking cessation aids
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
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
26442600
Citation
Di Ciano P, Guranda M, Lagzdins D, Tyndale RF, Gamaleddin I, Selby P, Boileau I, Le Foll B. Varenicline-Induced Elevation of Dopamine in Smokers: A Preliminary [(11)C]-(+)-PHNO PET Study. Neuropsychopharmacology. 2016 May;41(6):1513-20. doi: 10.1038/npp.2015.305. Epub 2015 Oct 7.
Results Reference
result
Links:
URL
http://www.camh.net/research
Description
Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

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The Effect of Varenicline on D2/D3 Receptor Binding in Smokers

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