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

Nicotine Dependence Clinical Trial

Official title:

Investigating the Effects of Varenicline on D2/3 Receptor Binding in Brain of Tobacco-smokers: a PET/[11C](+)PHNO Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01632189
• Other study ID #: 040/2012
• Status: Completed
• Phase: N/A
• First received: June 28, 2012
• Last updated: January 26, 2016
• Start date: September 2012
• Est. completion date: August 2015

Study information

• Verified date: January 2016
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 45 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Nicotine Dependence

Intervention

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.

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	Ontario Lung Association, Pfizer

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. 2015 Oct 7. doi: 10.1038/npp.2015.305. [Ep — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[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).	10 days	No
Secondary	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.	6 months	No

External Links

•   Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching