Imaging Extrastriatal Dopamine Release in Tobacco Smokers and Nonsmokers

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02348385
• Collaborator: (none)
• Enrollment: 49
• Location: 1
• Duration (Months): 60
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The goal is to examine sex differences in amphetamine-induced dopamine release in tobacco smokers and nonsmokers.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence	Drug: Amphetamine

Detailed Description

Aim 1:

To determine sex differences in amphetamine-induced dopamine (DA) release in healthy tobacco smokers and nonsmokers.

FLB-457 has been used in several PET centers and has recently been approved for use at the Yale University PET Center. We would like to determine whether there are sex differences in amphetamine induced DA release in healthy tobacco smokers and nonsmokers. Specifically, 40 healthy tobacco smokers and 40 healthy nonsmokers will have an magnetic resonance imaging (MRI) scan followed on another day by two FLB scans (ideally, the two PET scans will be carried out in the same day). Starting at 3 hours before the second PET scan, amphetamine (0.4mg/kg, PO) will be administered.

Aim 2:

To determine sex differences in amphetamine-induced dopamine release in tobacco smokers from Aim 1 after treatment with guanfacine. Guanfacine will be given under a different protocol. We plan to determine whether guanfacine treatment differentially inhibits amphetamine-induced DA release in men and smokers from Aim 1. After their first scan, the same 40 healthy tobacco smokers from Aim 1 will take guanfacine for 3 weeks under and then will have another set of FLB scans (ideally, the two PET scans will be carried out in the same day). Starting at 3 hours before the second PET scan, amphetamine (0.4mg/kg, PO) will be administered, as before. The sets of scans will be separated by at least 21 days, but due to scheduling and technical difficulties the second set may be scheduled up to 6 weeks after the first set.

Study Design

• Study Type: Observational
• Actual Enrollment: 49 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Imaging Extrastriatal Dopamine Release in Tobacco Smokers and Nonsmokers
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Healthy Tobacco Smokers There is only one arm to the study. All subjects will receive amphetamine	Drug: Amphetamine; Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.; Other Names: dextroamphetamine
Healthy Nonsmokers There is only one arm to the study. All subjects will receive amphetamine	Drug: Amphetamine; Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.; Other Names: dextroamphetamine

Outcome Measures

Primary Outcome Measures

1. Percent Change in Binding Potential of Dopamine Release During PET Scan Post Amphetamine Administration [After 2 PET Scans (1 day)]

   Percent change in binding potential of dopamine release during PET scan post amphetamine administration.Binding potential (BP) is the PET neuroimaging outcome measure that is computed as a proxy for availability of dopamine D2/3 receptors in a given region-of-interest.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

General 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 DSM-IV Axis 1 diagnosis in 2 preceding years)

• 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

• to participate in imaging studies including 2 PET scans and 1 MRI scan

• nonsmokers (smoked < 100 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 Fagerstrom score (FTND)>3, urine cotinine >150 ng/mL and carbon monoxide (CO) >12 ppm at intake)

General 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 at 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.

• Blood donation within 8 weeks of the start of the study.

• history of a bleeding disorder or are taking medication to thin their blood

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

• Yale University

Investigators

• Principal Investigator: Kelly Cosgrove, PhD, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 22, 2017

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT02348385
• Other Study ID Numbers: 1106008678
• First Posted: Jan 28, 2015
• Last Update Posted: Mar 18, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Yale University: amphetamine; cigarette smokers
• Additional relevant MeSH terms: Tobacco Use Disorder; Amphetamine; Dextroamphetamine

Study Results

Participant Flow

Arm/Group Title	Healthy Tobacco Smokers	Healthy Nonsmokers
Arm/Group Description	There is only one arm to the study. All subjects will receive amphetamine Amphetamine: Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	There is only one arm to the study. All subjects will receive amphetamine Amphetamine: Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.
Period Title: Overall Study
STARTED	24	25
COMPLETED	24	25
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Healthy Tobacco Smokers	Healthy Nonsmokers	Total
Arm/Group Description	Healthy Tobacco Smoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	Healthy Nonsmoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	Total of all reporting groups
Overall Participants	24	25	49
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	24 100%	25 100%	49 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	12 50%	12 48%	24 49%
Male	12 50%	13 52%	25 51%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 8.3%	3 12%	5 10.2%
Native Hawaiian or Other Pacific Islander	0 0%	1 4%	1 2%
Black or African American	11 45.8%	6 24%	17 34.7%
White	11 45.8%	15 60%	26 53.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	24 100%	25 100%	49 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Binding Potential of Dopamine Release During PET Scan Post Amphetamine Administration
Description	Percent change in binding potential of dopamine release during PET scan post amphetamine administration.Binding potential (BP) is the PET neuroimaging outcome measure that is computed as a proxy for availability of dopamine D2/3 receptors in a given region-of-interest.
Time Frame	After 2 PET Scans (1 day)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Male Healthy Tobacco Smokers	Male Healthy Nonsmokers	Female Healthy Tobacco Smokers	Female Healthy Nonsmokers
Arm/Group Description	Healthy Tobacco Smoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	Healthy Nonsmoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	Healthy Tobacco Smoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.	Healthy Tobacco Smoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.
Measure Participants	12	13	12	12
Mean (Standard Deviation) [percentage change in binding potential]	14 (4.3)	11.2 (2.4)	1.9 (3.0)	9.3 (3.3)

Adverse Events

Time Frame	Monitoring for adverse events was maintained from initial protocol approval to final subject participation, (5 years 4 months) Monitoring for each individual subject was maintained for at least one week after their final study visit or until any issues had resolved.
Adverse Event Reporting Description	No Reportable Adverse Events Occurred
Arm/Group Title	Healthy Tobacco Smokers		Healthy Nonsmokers
Arm/Group Description	Healthy Tobacco Smoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.		Healthy Nonsmoker Subjects will have 2 PET scans on the same day. Up to 3 hours before the second PET Scan, amphetamine (0.4mg/kg, orally) will be administered.
All Cause Mortality
	Healthy Tobacco Smokers		Healthy Nonsmokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)
Serious Adverse Events
	Healthy Tobacco Smokers		Healthy Nonsmokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Tobacco Smokers		Healthy Nonsmokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.