The Effect of Varenicline on D2/D3 Receptor Binding in Smokers
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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 |
- [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).
- 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.
| Estimated Enrollment: | 8 |
| Study Start Date: | September 2012 |
| Estimated Study Completion Date: | September 2013 |
| Estimated Primary Completion Date: | September 2013 (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
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 |
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| Contact: Bernard Le Foll, MD, PhD | 416-535-8501 ext 4772 | bernard.lefoll@camh.ca |
| Contact: Mihail Guranda, MD | 416-535-8501 ext 6733 | Mihail.Guranda@camh.ca |
| Canada, Ontario | |
| Centre for Addiction and Mental Health | Recruiting |
| Toronto, Ontario, Canada | |
| Contact: Bernard Le Foll, MD PhD 416-535-8501 ext 4772 Bernard.LeFoll@camh.ca | |
| Sub-Investigator: Isabelle Boileau, PhD | |
| Sub-Investigator: Peter Selby, MBBS | |
| Sub-Investigator: Alan Wilson, PhD | |
| Principal Investigator: Bernard Le Foll, MD, PhD | |
| 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: | April 4, 2013 |
| 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 May 16, 2013