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

This study has been withdrawn prior to enrollment.
(Technical complications.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Marc J. Kaufman, Mclean Hospital
ClinicalTrials.gov Identifier:
NCT01784016
First received: January 30, 2013
Last updated: May 22, 2014
Last verified: May 2014
  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.


Enrollment: 0
Study Start Date: January 2014
Study Completion Date: May 2014
Primary Completion Date: May 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
McLean Hospital
Belmont, Massachusetts, United States, 02478
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
Charlestown, Massachusetts, United States, 02129
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: May 22, 2014
Health Authority: United States: Food and Drug Administration
United States: Partners Human Research Committee
United States: McLean Hospital Institutional Review Board

ClinicalTrials.gov processed this record on September 22, 2014