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

This study has been completed.
Sponsor:
Collaborators:
Ontario Lung Association
Pfizer
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01632189
First received: June 28, 2012
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Nicotine Dependence
Drug: Varenicline

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Investigating the Effects of Varenicline on D2/3 Receptor Binding in Brain of Tobacco-smokers: a PET/[11C](+)PHNO Study

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • [11C]-(+)-PHNO DRD2/3 binding potential (BPND) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Relationship between clinical ratings of abstinence and cravings and DRD2/3 normalization after 10-day course of varenicline administration.


Enrollment: 8
Study Start Date: September 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Varenicline
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.
Drug: Varenicline
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.
Other Name: Champix

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.

  Eligibility

Ages Eligible for Study:   21 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01632189

Locations
Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
Sponsors and Collaborators
Centre for Addiction and Mental Health
Ontario Lung Association
Pfizer
Investigators
Principal Investigator: Bernard Le Foll, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Bernard Le Foll, Principal Investigator; MD, PhD, CCFP, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01632189     History of Changes
Other Study ID Numbers: 040/2012
Study First Received: June 28, 2012
Last Updated: January 20, 2014
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
Varenicline
PET imaging
[11C]-(+)-PHNO PET
neuroimaging in smokers

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Mental Disorders
Varenicline
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014