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Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion Paradigm (phno_amth)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kelly Cosgrove, Yale University
ClinicalTrials.gov Identifier:
NCT01699607
First received: October 1, 2012
Last updated: April 6, 2016
Last verified: April 2016
  Purpose
A research study designed to examine amphetamine-induced dopamine release using the PET imaging agent [11C]PHNO in tobacco smokers while currently smoking and during acute withdrawal and in nonsmokers. Twenty healthy men and women tobacco smokers and twenty healthy nonsmokers will be recruited. Each subject will participate in 1 MRI and up to 2 [11C]PHNO PET scans. On the study day subjects will participate in two [11C]PHNO scans (ideally, the two PET scans will be carried out in the same day). Three hours before the second PET scan, amphetamine (0.5 mg/kg, PO) will be administered. In smokers, the scan will occur at 10-21 days of smoking abstinence.

Condition Intervention
Nicotine Dependence,
Healthy
Drug: Amphetamine

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change in Dopamine Levels at Baseline and After Amphetamine Administration as Measured by Percent Change in PET Tracer Binding Potential. [ Time Frame: first 90 minute scan at baseline, second 90 minute scan start 150 minutes post amphetamine administration ] [ Designated as safety issue: No ]
    PET images will be obtained in subjects at baseline and after amphetamine administration. Dopamine release will be measured as a percent change in binding potential. Increased dopamine release will result in decreased radiotracer binding because dopamine will displace the radiotracer.


Enrollment: 10
Study Start Date: June 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: amphetamine
There is only one arm to the study. All subjects will receive amphetamine at 0.5mg/kg prior to the second PET scan.
Drug: Amphetamine
All subjects will receive amphetamine to induce elevated dopamine levels in the brain at 0.5mg/kg
Other Name: dextro-amphetamine

Detailed Description:

To determine amphetamine-induced DA release in tobacco smokers while currently smoking and during acute withdrawal and in nonsmokers. Twenty healthy men and women tobacco smokers and twenty healthy nonsmokers will be recruited. Each subject will participate in 1 MRI and up to 2 [11C]PHNO PET scans. On the PET study day subjects will participate in two [11C]PHNO scans (ideally, the two PET scans will be carried out in the same day). Three hours before the second PET scan, amphetamine (0.5 mg/kg, PO) will be administered. In smokers, the set of scans will occur at 10-21 days of smoking abstinence. Smoking abstinence will be determined by carbon monoxide and urine cotinine (a breakdown product of nicotine in cigarette smoke) levels. Subjects will be asked to breathe into a breathalyzer to measure carbon monoxide and to provide a urine sample to measure cotinine. Smoking abstinence will be confirmed by carbon monoxide and cotinine levels that are reduced as compared to actively smoking. We hypothesize that smokers at 10-21 days of withdrawal will have amphetamine-induced DA release that is blunted compared to healthy nonsmokers.

Magnetic resonance imaging (MRI) scans (3 T) will be collected in each subject to co-register PET and MRI for image analysis. Within two weeks of the PET study, an MRI will be acquired at the Yale University MRI Center. Subjects will be taken through a ferromagnetic metal detector before entering the scan room. The acquisition sequence is a 3D fast spoiled grass (FSPGR) MR pulse sequence with an IR prep of 300 ms. (TE= 3.3 ms, flip angle=17 degrees; slice thickness= 1.2 mm) optimized for delineating gray matter/white matter/CSF boundaries. The small voxel size (0.93 X 1.2 X 0.93 mm) provides high-resolution volumetric images. MR images provide a matching anatomical atlas for creating individualized region-of-interest templates for each subject.

Subject preparation consists of two intravenous (IV) catheterizations and immobilization of the head. PET scans are acquired as subjects rest using an HRRT PET scanner (207 slices, resolution better than 3 mm FWHM). This resolution permits visualization of the PHNO and raclopride uptake in the ventral/dorsal striatum, in globus pallidus (GP) and substantia nigra (SN). A transmission scan using an orbiting 137Cs point-source is obtained for each emission scan. Motion correction will be performed dynamically with measurements from the Vicra (NDI Systems, Waterloo, Ontario) used by a dedicated list-mode reconstruction algorithm.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • men and women, aged 18-55 years
  • who are able to read and write
  • who are able to give voluntary written informed consent
  • have no current uncontrolled medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology
  • have no history of a neurological or psychiatric disorder, e.g., no DSMIV Axis 1 diagnosis in 2 preceding years, except nicotine dependence in smokers)
  • drink less than 21 drinks/week for women and less than 35 drinks per week for men
  • have not used marijuana in the past 30 days and have not met criteria for dependence in the past 2 years
  • do not suffer from claustrophobia or any MRI contradictions
  • nonsmokers (smoked < 40 cigarettes in lifetime with urinary cotinine levels 0-30 ng/mL both at intake evaluation and on scan day)
  • smokers (smoked at least 10 cigarettes/day for at least one year with an FTND>3, urine cotinine >150 ng/mL and CO >12 ppm at intake)

Exclusion Criteria:

  • psychosis
  • presence of acute or unstable medical or neurological illness. Subjects will be excluded from the study if they present with any history of serious medical or neurological illness or if they show signs of a major medical or neurological illness on examination or lab testing including history of seizures, head injury, brain tumor, heart, liver or kidney disease, eating disorder, diabetes.
  • regular use of any psychotropic drugs including anxiolytics and antidepressants and other over-the-counter medications and herbal products within the last six months
  • pregnancy/breast feeding (as documented by pregnancy testing at screening or on days of the imaging studies),
  • suicidal ideation or behavior
  • pacemaker or other ferromagnetic material in body.
  • use of medications which affect dopamine transmission within 2 weeks of the PET study
  • participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for normal volunteers
  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: NCT01699607

Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06519
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Kelly Cosgrove, Ph.D. Assistant Professor
  More Information

Responsible Party: Kelly Cosgrove, Assistant Professor, Yale University
ClinicalTrials.gov Identifier: NCT01699607     History of Changes
Other Study ID Numbers: 0910005822 
Study First Received: October 1, 2012
Results First Received: July 14, 2015
Last Updated: April 6, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Yale University:
Cigarette Smokers
Healthy Non Smokers
Amphetamine
PET
Controls

Additional relevant MeSH terms:
Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Amphetamine
Dextroamphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016