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

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ClinicalTrials.gov Identifier: NCT01699607
Recruitment Status : Completed
First Posted : October 3, 2012
Results First Posted : September 18, 2015
Last Update Posted : February 9, 2017
Sponsor:
Information provided by (Responsible Party):
Kelly Cosgrove, Yale University

Tracking Information
First Submitted Date  ICMJE October 1, 2012
First Posted Date  ICMJE October 3, 2012
Results First Submitted Date  ICMJE July 14, 2015
Results First Posted Date  ICMJE September 18, 2015
Last Update Posted Date February 9, 2017
Study Start Date  ICMJE June 2012
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
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 ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT01699607 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion Paradigm
Official Title  ICMJE Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE
  • Nicotine Dependence
  • Healthy
Intervention  ICMJE Drug: Amphetamine
All subjects will receive amphetamine to induce elevated dopamine levels in the brain at 0.5mg/kg
Other Name: dextro-amphetamine
Study Arms  ICMJE 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.
Intervention: Drug: Amphetamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 18, 2015)
10
Original Estimated Enrollment  ICMJE
 (submitted: October 2, 2012)
40
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01699607
Other Study ID Numbers  ICMJE 0910005822
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kelly Cosgrove, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Kelly Cosgrove, Ph.D. Assistant Professor
PRS Account Yale University
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP