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

This study is not yet open for participant recruitment.
Verified October 2013 by Mclean Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Marc J. Kaufman, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01784016
First received: January 30, 2013
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Nicotine Dependence
Smoking Cue Reactivity
Relapse to Smoking
Radiation: [11C]-PHNO
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Concurrent PET D2/D3 Receptor Imaging and fMRI Smoking Cue Reactivity in Smokers

Resource links provided by NLM:


Further study details as provided by Mclean Hospital:

Primary Outcome Measures:
  • Dopamine D3 Receptor Binding Potential Difference Between Smokers and Nonsmokers [ Time Frame: March 2014 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Smoking Cue fMRI Reactivity Association with Dopamine D3 Receptor Binding Potential [ Time Frame: March 2014 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 45
Study Start Date: January 2014
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy Smokers
Healthy smokers aged 18-50 years reporting average cigarette consumption of 15 or more cigarettes/day for the past year, providing an expired breath carbon monoxide reading exceeding 10 ppm at screening.
Radiation: [11C]-PHNO
[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Other Name: 11C-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol
Experimental: Healthy Nonsmokers
Healthy nonsmoking controls aged 18-50 reporting consumption of <100 cigarettes in their lifetime, none in the last 6 months, providing an exhaled breath carbon monoxide reading of < 9 ppm at screening.
Radiation: [11C]-PHNO
[11C]-PHNO will be administered once intravenously to conduct Positron Emission Tomography (PET) measurements of dopamine D2/D3 binding potential.
Other Name: 11C-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01784016

Contacts
Contact: Marc J Kaufman, Ph.D. 617-855-3469 kaufman@mclean.harvard.edu

Locations
United States, Massachusetts
McLean Hospital Not yet recruiting
Belmont, Massachusetts, United States, 02478
Principal Investigator: Marc J. Kaufman, Ph.D.         
Sub-Investigator: Amy C. Janes, Ph.D.         
Sub-Investigator: Blaise deB. Frederick, Ph.D.         
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: A. Eden Evins, M.D., M.P.H.         
Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging Not yet recruiting
Charlestown, Massachusetts, United States, 02129
Sub-Investigator: Jacob Hooker, Ph.D.         
Sub-Investigator: Ciprian Catana, M.D., Ph.D.         
Sponsors and Collaborators
Mclean Hospital
Investigators
Principal Investigator: Marc J. Kaufman, Ph.D. Mclean Hospital
  More Information

Publications:

Responsible Party: Marc J. Kaufman, Director, Translational Imaging Laboratory, McLean Hospital, Mclean Hospital
ClinicalTrials.gov Identifier: NCT01784016     History of Changes
Other Study ID Numbers: SmokingPETD2-3fMRI, R21DA031925-01A1
Study First Received: January 30, 2013
Last Updated: October 28, 2013
Health Authority: United States: Food and Drug Administration
United States: Partners Human Research Committee
United States: McLean Hospital Institutional Review Board

Additional relevant MeSH terms:
Tobacco Use Disorder
Smoking
Substance-Related Disorders
Mental Disorders
Habits

ClinicalTrials.gov processed this record on April 17, 2014