Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans

Tobacco Use Disorder Clinical Trial

Official title:

Does the Insula Control Smoking-induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans. Part I: Smoking-induced Dopamine Release: a [11C]-(+)-PHNO PET Study in Humans.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01302262
• Other study ID #: 143/2010
• Status: Completed
• Phase: N/A
• First received: February 22, 2011
• Last updated: March 4, 2013
• Start date: February 2011
• Est. completion date: March 2013

Study information

• Verified date: March 2013
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Observational

Clinical Trial Summary

This study will evaluate effects of smoking on the dopaminergic system by using PET tomography with new radioligand, [11C]-(+)-PHNO. Our primary hypothesis is that smoking a cigarette will produce dopamine release and this release can be measured using PET imaging and the [11C]-(+)-PHNO radiotracer. The secondary hypothesis is that this smoking induced dopamine release will be correlated with subjective craving and anxiety ratings.

Description:

This will be a within-subjects study in healthy male and female smokers. There will be one within factor condition: Smoking and Non Smoking. Therefore, there will be a repeated measure of PET scans using [11C]-(+)-PHNO under two different conditions. Ten subjects (n=5 male and n=5 female) included in the study will come on two different days and will have a Smoking or Non smoking session performed just before the PET study. Subjective assessments will be conducted at each experimental condition.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Adult males or females

• Regular smoking of at least 10 cigarettes, excluding ultra-low nicotine cigarettes, per day for at least two years

• Score on the Fagerstrom Test for Nicotine Dependence of 4 or more

• No intention to quit or reduce tobacco use, and no treatment for tobacco dependence currently

• No history of abuse of or dependence on any other drug, defined by DSM-IV criteria

Exclusion Criteria:

• Pregnancy

• Presence of metal objects in the body or implanted electronic devices, that preclude safe MR scanning

• Claustrophobia

• Cardiovascular or cerebrovascular diseases

• Major psychiatric disorders including mood, anxiety or psychotic disorders

• 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 (e.g. neuroleptics, bupropion)

• Learning disability, amnesia or other conditions that impede memory and attention

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Tobacco Use Disorder

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health - 33 Russell St	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health	Pfizer

Country where clinical trial is conducted

Canada, 

References & Publications (7)

Boileau I, Guttman M, Rusjan P, Adams JR, Houle S, Tong J, Hornykiewicz O, Furukawa Y, Wilson AA, Kapur S, Kish SJ. Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease. Brain. 2009 May;132(Pt 5):1366-75. doi: 10.1093/brain/awn337. Epub 2009 Jan 19. — View Citation

Brody AL, Mandelkern MA, Olmstead RE, Scheibal D, Hahn E, Shiraga S, Zamora-Paja E, Farahi J, Saxena S, London ED, McCracken JT. Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens. Arch Gen Psychiatry. 2006 Jul;63(7):808-16. — View Citation

Brody AL, Olmstead RE, London ED, Farahi J, Meyer JH, Grossman P, Lee GS, Huang J, Hahn EL, Mandelkern MA. Smoking-induced ventral striatum dopamine release. Am J Psychiatry. 2004 Jul;161(7):1211-8. — View Citation

Le Foll B, Goldberg SR, Sokoloff P. Dopamine D3 receptor ligands for the treatment of tobacco dependence. Expert Opin Investig Drugs. 2007 Jan;16(1):45-57. Review. — View Citation

Le Foll B, Goldberg SR, Sokoloff P. The dopamine D3 receptor and drug dependence: effects on reward or beyond? Neuropharmacology. 2005 Sep;49(4):525-41. Review. — View Citation

Le Foll B, Schwartz JC, Sokoloff P. Dopamine D3 receptor agents as potential new medications for drug addiction. Eur Psychiatry. 2000 Mar;15(2):140-6. — View Citation

Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, Houle S, Seeman P, Ginovart N. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem. 2005 Jun 16;48(12):4153-60. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[11C]-(+)-PHNO binding potential	The process of imaging requires the injection of a positron-emitting radiotracer (here, [11C]-(+)-PHNO) that binds to the protein of interest (here, dopamine receptor DRD2/3) followed by the measurement of this binding using the PET scanner. Dopamine release increases DRD 2/3 occcupancy which results in decreased radiotracer's binding potential, and vice versa. [11C]-(+)-PHNO binding potential will be measured on two different conditions (Smoking vs. Non-smoking) on two separate days.	Up to 14 days between PET scans	No
Secondary	Subjective reports of craving	Levels of subjective craving will be assessed prior to and after each condition (Smoking vs. Non-smoking) on two separate days. Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire of Smoking Urges, The Urge to Smoke scale, Tobacco Craving Questionnaire, and 21-item Visual Analogue Scale will be used.	Up to 14 days between PET scans	No
Secondary	Subjective reports of anxiety	Subjective reports of anxiety will be collected prior to and after each condition (Smoking vs. Non-smoking) on two separate days. State anxiety questions from the Spielberg State-Trait Anxiety Inventory will be used.	Up to 14 days between PET scans	No

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