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 : March 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|Nicotine Dependence Healthy||Drug: Amphetamine||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Test-retest Reproducibility of [11C]PHNO PET Using the Constant Infusion|
|Study Start Date :||June 2012|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||July 2013|
There is only one arm to the study. All subjects will receive amphetamine at 0.5mg/kg prior to the second PET scan.
All subjects will receive amphetamine to induce elevated dopamine levels in the brain at 0.5mg/kg
Other Name: dextro-amphetamine
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01699607
|United States, Connecticut|
|New Haven, Connecticut, United States, 06519|
|Principal Investigator:||Kelly Cosgrove, Ph.D.||Assistant Professor|