SmokeAtt02: Neuroimaging Decision Making and Response Inhibition During Smoking Abstinence

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00672256
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 62
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The broad objective of this proposal is to identify functional neuroanatomical correlates of impairments in response inhibition during smoking abstinence. We will measure changes in performance and regional blood oxygenation levels using functional magnetic resonance imaging (fMRI)while smokers complete tasks designed to assess decision making and response inhibition.

Our primary hypothesis is that smoking abstinence will result in impaired response inhibition accompanied by decreases in blood-oxygenation-level-dependent (BOLD) fMRI signal in brain regions associated with these cognitive processes including frontal cortex and the ventral striatum. Abstinence may also result in performance-related increases in activation in brain regions associated with effortful processing including the anterior cingulate cortex in effort to compensate for deficits in other regions.

Condition or Disease	Intervention/Treatment	Phase
Smoking	Behavioral: Smoking Abstinence	N/A

Detailed Description

Participants will learn and practice a Go/No-Go reaction time task (Garavan, Hester, Murphy, Fassbender, & Kelly, 2006) that measures inhibitory and excitatory aspects of behavioral control. During the task subjects are presented with an alternating series of Xs and Ys in the center of the screen and must press a button every time they see a Go trial (the letter 'Y' or the letter 'X') while inhibiting a response when they are presented with a No-Go trial (any interruption of the X Y alternating stream, e.g., X Y Y).

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Neuroimaging Decision Making and Response Inhibition During Smoking Abstinence
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Smokers not interested in quitting smoking Smokers were scanned 24 hours after quitting smoking, and scanned after smoking as usual.	Behavioral: Smoking Abstinence; Smokers were scanned after having quitting smoking for 24 hours, and scanned after smoking as usual.

Outcome Measures

Primary Outcome Measures

1. Signal Change in Functional Magnetic Resonance Imaging (fMRI) BOLD Signal Between Response Inhibition Trials and Control Trials in Right Inferior Frontal Cortex (rIFC) During Task on Satiated Day [12.5 minutes of fMRI scanning following smoking as usual]

   Percent signal change in fMRI BOLD response in rIFC to correctly inhibited targets (as compared to control trials) during a response inhibition task following smoking as usual. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.

2. Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Right Inferior Frontal Cortex (rIFC) During Task on Abstinent Day [12.5 minutes of fMRI scanning following 24 hrs smoking abstinence]

   Percent signal change in fMRI BOLD response in rIFC to correctly inhibited targets (as compared to control trials) during a response inhibition task following not smoking for 24 hours. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.

3. Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Presupplementary Motor Area (Pre-SMA) During Task on Abstinent Day [12.5 minutes of fMRI scanning following 24 hrs smoking abstinence]

   Percent signal change in fMRI BOLD response in pre-SMA to correctly inhibited targets (as compared to control trials) during a response inhibition task following not smoking for 24 hours. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.

4. Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Presupplementary Motor Area (Pre-SMA) During Task on Satiated Day [12.5 minutes of fMRI scanning following smoking as usual]

   Percent signal change in fMRI BOLD response in pre-SMA to correctly inhibited targets (as compared to control trials) during a response inhibition task following smoking as usual. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Smoker subjects must have

• smoked an average of 10 cigarettes per day for two continuous years of a brand that delivers (by Federal Trade Commission rated yields) at least 0.5 mg nicotine

• have an expired air carbon monoxide reading of at least 10 ppm.

• must be in general good health

Non-smoker subjects must have

• smoked less than 50 cigarettes in their lifetime

• have not smoked in the last six months

• have an expired air carbon monoxide reading of less than or equal to 5 ppm.

• must be in general good health.

Exclusion Criteria:

• major medical condition

• anything that would make participation unsafe (e.g., have pacemaker or other metallic implant) or uncomfortable (e.g., chronic pain)

• psychiatric condition

• suffering from claustrophobia

• current alcohol or drug abuse

• smokeless tobacco use, or use of nicotine replacement therapy or other smoking cessation treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Duke University
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Francis J McClernon, Ph.D, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00672256
• Other Study ID Numbers: Pro00011917; DA017261; 9270
• First Posted: May 6, 2008
• Last Update Posted: Jul 23, 2014
• Last Verified: Mar 1, 2013

• Keywords provided by Duke University: Smoking; fMRI

Study Results

Participant Flow

Recruitment Details	community recruitment completed recruitment March 2009
Pre-assignment Detail	enrolled participants would be excluded if they were unable to meet study requirements, or had scheduling issues.

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Period Title: Overall Study
STARTED	62
COMPLETED	18
NOT COMPLETED	44

Baseline Characteristics

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Overall Participants	62
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	62 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.5 (10.03)
Sex: Female, Male (Count of Participants)
Female	27 43.5%
Male	35 56.5%
Region of Enrollment (participants) [Number]
United States	62 100%

Outcome Measures

1. Primary Outcome

Title	Signal Change in Functional Magnetic Resonance Imaging (fMRI) BOLD Signal Between Response Inhibition Trials and Control Trials in Right Inferior Frontal Cortex (rIFC) During Task on Satiated Day
Description	Percent signal change in fMRI BOLD response in rIFC to correctly inhibited targets (as compared to control trials) during a response inhibition task following smoking as usual. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.
Time Frame	12.5 minutes of fMRI scanning following smoking as usual

Outcome Measure Data

Analysis Population Description

18 participants completed all aspects of the study. Two participants were excluded from analyses because they reported falling asleep in the scanner and one was excluded because of an incidental finding during the scan.

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Measure Participants	15
Mean (Standard Deviation) [percentage of signal change]	0.039 (0.099)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Smokers
	Comments	Within group repeated measures design. Null hypothesis is that there will be no difference in percent signal change during active task relative to baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.039
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Right Inferior Frontal Cortex (rIFC) During Task on Abstinent Day
Description	Percent signal change in fMRI BOLD response in rIFC to correctly inhibited targets (as compared to control trials) during a response inhibition task following not smoking for 24 hours. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.
Time Frame	12.5 minutes of fMRI scanning following 24 hrs smoking abstinence

Outcome Measure Data

Analysis Population Description

18 participants completed all aspects of the study. Two participants were excluded from analyses because they reported falling asleep in the scanner and one was excluded because of an incidental finding during the scan.

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Measure Participants	15
Mean (Standard Deviation) [percentage of signal change]	0.104 (0.141)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Smokers
	Comments	Within group repeated measures design. Null hypothesis is that there will be no difference in percent signal change during active task relative to baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.104
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Presupplementary Motor Area (Pre-SMA) During Task on Abstinent Day
Description	Percent signal change in fMRI BOLD response in pre-SMA to correctly inhibited targets (as compared to control trials) during a response inhibition task following not smoking for 24 hours. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.
Time Frame	12.5 minutes of fMRI scanning following 24 hrs smoking abstinence

Outcome Measure Data

Analysis Population Description

18 participants completed all aspects of the study. Two participants were excluded from analyses because they reported falling asleep in the scanner and one was excluded because of an incidental finding during the scan.

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Measure Participants	15
Mean (Standard Deviation) [percentage of signal change]	0.173 (0.123)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Smokers
	Comments	Within group repeated measures design. Null hypothesis is that there will be no difference in percent signal change during active task relative to baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.173
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Signal Change in fMRI BOLD Signal Between Response Inhibition Trials and Control Trials in Presupplementary Motor Area (Pre-SMA) During Task on Satiated Day
Description	Percent signal change in fMRI BOLD response in pre-SMA to correctly inhibited targets (as compared to control trials) during a response inhibition task following smoking as usual. Response inhibition trials are trials in the task in which the participant must inhibit a response (not press the button)when presented with a No-Go trial. Control trials are trials in the task in which the participant must press the button when presented with a Go trial.
Time Frame	12.5 minutes of fMRI scanning following smoking as usual

Outcome Measure Data

Analysis Population Description

18 participants completed all aspects of the study. Two participants were excluded from analyses because they reported falling asleep in the scanner and one was excluded because of an incidental finding during the scan.

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
Measure Participants	15
Mean (Standard Deviation) [percentage of signal change]	0.169 (0.170)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Smokers
	Comments	Within group repeated measures design. Null hypothesis is that there will be no difference in percent signal change during active task relative to baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.169
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Smokers
Arm/Group Description	Men and women ages 18-50 who smoke at least 10 cigarettes per day of a brand delivery at least 0.5 mg of nicotine for at least 2 years.
All Cause Mortality
	Smokers
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Smokers
	Affected / at Risk (%)	# Events
Total	00/18 (0%)
Other (Not Including Serious) Adverse Events
	Smokers
	Affected / at Risk (%)	# Events
Total	00/18 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.