Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

Nicotine Dependence Clinical Trial

Official title:

Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01784016
• Other study ID #: SmokingPETD2-3fMRI
• Secondary ID: R21DA031925-01A1
• Status: Withdrawn
• Phase: Phase 1
• First received: January 30, 2013
• Last updated: May 22, 2014
• Start date: January 2014
• Est. completion date: May 2014

Study information

• Verified date: May 2014
• Source: Mclean Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Partners Human Research CommitteeUnited States: McLean Hospital Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This trial aims to determine whether dopamine D3 receptors are elevated in smokers versus nonsmokers and whether correlations exist between D3 receptor binding potential (BP) and functional MRI (fMRI) reactivity to smoking cues, which has been associated with smoking relapse vulnerability.

Neuroimaging measures of D3 BP and smoking cue fMRI reactivity will be collected concurrently in otherwise healthy nicotine-dependent smokers and age-matched nonsmokers using a 3 Tesla MRI scanner configured to conduct fMRI and Positron Emission Tomography (PET).

We will measure D3 receptor BP using radiolabeled [11C]-(+)-PHNO, which has a relatively higher affinity for D3 versus D2 receptors.

We hypothesize that D3 BP will be elevated in smokers versus nonsmokers and that in smokers, there will be a positive correlation between smoking cue fMRI reactivity and D3 BP.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• competent to provide written informed consent

• Smokers: self-report of smoking 15 or more cigarettes/day for the past year, self-report of smoking first cigarette of the day within 30 minutes of awakening, meets DSM-IV criteria for Nicotine Dependence, provides expired breath carbon monoxide reading of > 10 ppm at enrollment

• Nonsmokers: self-report of consuming <100 cigarettes in their lifetime, none in the last 6 months, provides expired breath carbon monoxide reading of < 9 ppm at enrollment

• Women of childbearing potential: negative STAT serum beta-human chorionic gonadotrophin pregnancy test before scanning

Exclusion Criteria:

• pregnant or able to become pregnant and not willing to undergo blood pregnancy test

• unstable medical illness with likely hospitalization for treatment within 6 months

• life-threatening arrhythmia, cerebro-vascular or cardiovascular event within 6 months of enrollment; liver function tests elevated over 2.5x normal; CNS tumor or seizure disorder

• users of other tobacco- or nicotine-containing products (gum, patches, e-cigarettes)

• lifetime history of DSM-IV bulimia, organic mental disorder, brain injury or psychotic disorder

• 6 month history of non-nicotine substance use disorder or major depression

• history of multiple adverse drug reactions

• current use of excluded concomitant medications (smoking cessation medications)

• known history of allergic reaction to the PET ligand [11C]-PHNO, its components, or any medication

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Nicotine Dependence
• Relapse to Smoking
• Smoking Cue Reactivity

Intervention

Radiation:
• [11C]-PHNO
[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.

Locations

Country	Name	City	State
United States	McLean Hospital	Belmont	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging	Charlestown	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mclean Hospital	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Janes AC, Pizzagalli DA, Richardt S, deB Frederick B, Chuzi S, Pachas G, Culhane MA, Holmes AJ, Fava M, Evins AE, Kaufman MJ. Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biol Psychiatry. 2010 Apr 15;67(8):722-9. doi: 10.1016/j.biopsych.2009.12.034. Epub 2010 Feb 20. Erratum in: Biol Psychiatry. 2010 May 15;67(10):1002. — View Citation

Le Foll B, Diaz J, Sokoloff P. Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse. 2003 Mar;47(3):176-83. — View Citation

Pak AC, Ashby CR Jr, Heidbreder CA, Pilla M, Gilbert J, Xi ZX, Gardner EL. The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions. Int J Neuropsychopharmacol. 2006 Oct;9(5):585-602. Epub 2006 Aug 31. — View Citation

Searle G, Beaver JD, Comley RA, Bani M, Tziortzi A, Slifstein M, Mugnaini M, Griffante C, Wilson AA, Merlo-Pich E, Houle S, Gunn R, Rabiner EA, Laruelle M. Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist. Biol Psychiatry. 2010 Aug 15;68(4):392-9. doi: 10.1016/j.biopsych.2010.04.038. — View Citation

Tziortzi AC, Searle GE, Tzimopoulou S, Salinas C, Beaver JD, Jenkinson M, Laruelle M, Rabiner EA, Gunn RN. Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage. 2011 Jan 1;54(1):264-77. doi: 10.1016/j.neuroimage.2010.06.044. Epub 2010 Jun 30. — 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	Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers	We will determine whether dopamine D3 receptor binding potential, a dimensionless number which represents the relative concentration of dopamine D3 receptors available for binding, is elevated in smokers versus nonsmoking controls.	March 2014	No
Secondary	Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential	In smokers, we will determine whether an association exists between smoking cue fMRI reactivity intensity (beta weight) and dopamine D3 receptor binding potential, a relationship between receptor (D3) density and dopamine occupancy.	March 2014	No