Trial Outcomes & Findings for Brain Imaging in Tobacco Smokers During a Quit Attempt (NCT NCT04055467)

Results Overview

Distribution volume (VT) in volumes of interest (VOI) in tobacco smokers. VOI are cingulate, hippocampus, frontal cortex, amygdala, and ventral striatum. VOI are defined via each individual subject's Magnetic Resonance Imaging for anatomical identification of the VOI for alignment with PET images.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

1 day

Results posted on

2024-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	Tobacco Smokers During a Quit Attempt Abstinent tobacco smokers receive a MRI and a PET scan with the alpha7-nAChR radiotracer \[18F\]-ASEM to assess alpha-7-nicotinic acetylcholine receptor availability and are incentivized for successfully abstaining from cigarettes for up to 8 days. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Overall Study STARTED	15
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Brain Imaging in Tobacco Smokers During a Quit Attempt

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tobacco Smokers During a Quit Attempt n=15 Participants Abstinent tobacco smokers receiving a MRI and a PET scan with the alpha7-nAChR radiotracer \[18F\]-ASEM to assess alpha-7-nicotinic acetylcholine receptor availability and are incentivized for successfully abstaining from cigarettes for up to 8 days. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Age, Continuous	36 Years STANDARD_DEVIATION 5.257 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Cigarettes per day at intake	15.875 Cigarettes per day STANDARD_DEVIATION 4.673 • n=5 Participants

PRIMARY outcome

Timeframe: 1 day

Population: 3 participants completed this study. No historical controls were matched, data not collected.

Distribution volume (VT) in volumes of interest (VOI) in tobacco smokers. VOI are cingulate, hippocampus, frontal cortex, amygdala, and ventral striatum. VOI are defined via each individual subject's Magnetic Resonance Imaging for anatomical identification of the VOI for alignment with PET images.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan Amygdala	22.640 mL/cm^3 Standard Deviation 1.717
Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan Cingulate	21.588 mL/cm^3 Standard Deviation 2.023
Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan Frontal cortex	22.226 mL/cm^3 Standard Deviation 2.522
Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan Hippocampus	17.431 mL/cm^3 Standard Deviation 0.213
Distribution Volume (VT) as Determined by [18F]-ASEM PET Scan Ventral striatum	20.454 mL/cm^3 Standard Deviation 1.562

PRIMARY outcome

Timeframe: 1 day

Population: Data are from the 3 study completers who completed the PET scan following 1 day of abstinence.

Self-report form has a 15-item list of symptoms where subjects self-rate symptom severity on a scale of 0-4. Validated symptoms for tobacco withdrawal in smokers will be used for the study to quantify total withdrawal symptoms at baseline (smoking as usual), when compared to symptoms on the day of the PET scan. Scores for each item range from 0-4, with 0 representing no symptoms and 4 representing severe withdrawal symptoms. The score range for validated symptoms is 0-36. Higher scores indicate greater nicotine withdrawal severity. Results reported are scores from day of PET scan.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Total Withdrawal Score on the Minnesota Nicotine Withdrawal Scale (MNWS) on Day of PET Scan	10.667 score on a scale Standard Deviation 1.528

PRIMARY outcome

Timeframe: 1 day

Population: Study Completers

The QSU is a 10-item questionnaire to measure craving/urges to smoke. For each item, subjects rate how strongly the subject feel "right now" on a Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Items are summed to yield two factor scores, Factor 1 Intention/desire to smoke (minimum score=5, maximum score=35), and Factor 2: Relief of negative affect and Urgent desire to smoke (minimum score=5, maximum score=35). Factor 1 and Factor 2 scores are combined, with a score range of 10-70, higher score indicating maximum cravings/urges to smoke (worse). Results reported reflect QSU scores on day of PET scan vs baseline.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Craving/Urge to Smoke as Determined Via the Questionnaire of Subjective Urges (QSU) on Day of PET Scan Day of PET	42.667 score on a scale Standard Deviation 6.429
Craving/Urge to Smoke as Determined Via the Questionnaire of Subjective Urges (QSU) on Day of PET Scan Baseline	22.7 score on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: 3 months

Population: Study Completers

Self-reported number of cigarettes smoked daily using a calendar-based time line method for past 90-days (i.e., time line follow back method) when smoking as usual. Average number of daily cigarettes smoked calculated using past 90 days (3 months).

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Cigarettes Smoked Per Day	17.00 Cigarettes per day Standard Deviation 3.00

SECONDARY outcome

Timeframe: 1 day

Population: Of the 3 completers all maintained abstinence for 1 day and relapsed to smoking (i.e., has CO above criteria levels) on the day after the pet scan.

Number of days abstinent (collected on day of PET scan) will be determined from counting number of CO-and cotinine-verified abstinence days. Abstinence will be defined as negative breath carbon oxide (CO)6ppm or lower AND urinary cotinine decreased by 25 percent from prior sample or \<100 ng/ml.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Number of Days of Smoking Abstinence on Day of PET Scan	1 Days Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, Day of PET

Consists of two 10-item mood scales to provide independent measures of positive and negative affect. Scores for negative affect subscale when smoking as usual, will be compared to days of CO and/or cotinine verified abstinence. Negative Affect Score: Add the scores on items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores can range from 0 - 40, with lower scores representing lower levels of negative affect.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Negative Mood as Determined by the Positive and Negative Affect Scale (PANAS) PET day	4.7 score on a scale Standard Deviation 2.9
Negative Mood as Determined by the Positive and Negative Affect Scale (PANAS) baseline	5.7 score on a scale Standard Deviation 1.5

SECONDARY outcome

Timeframe: Baseline, Day of PET

In this computerized task, a stimuli are presented, and subjects are instructed to respond as fast as possible to a specific target stimuli (X) and refrain from responding to more rarely occurring non-target stimuli (non-X). Inattention is indicated by high numbers of omissions and long reaction times. Omissions result from the failure to respond to target letters (i.e., non-Xs); omissions and reaction times when smoking as usual will be compared to those on visits 1-6 during the quit attempt abstinence days. Higher score for detectability represents worse sustained attention. Score range 0 to 100 with higher score being worse.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Attention as Assessed by Connors Continuous Performance Task Baseline	43.3 score on a scale Standard Deviation 6.0
Attention as Assessed by Connors Continuous Performance Task PET day	50 score on a scale Standard Deviation 13.5

SECONDARY outcome

Timeframe: Baseline, Day of PET

The number of correct responses for each trial of the Paced Serial Addition Task (PASAT); Involves presenting a series of single digit numbers where the two most recent digits must be summed. The participant must respond prior to the presentation of the next digit for a response to be scored as correct. Minimum score is 0 and maximum score is 120, with a lower number representing lower levels of sustained attention.The number of correct responses for each trial (maximum = 60). Data reported are the total (sum) correct responses for 2 trials.

Outcome measures

Outcome measures
Measure	[F18]-ASEM + Contingency Management n=3 Participants PET radiopharmaceutical 3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6 \[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide with incentive payments. \[F18\]-ASEM (3-(1,4-diazabicyclo\[3.2.2\]nonan-4-yl)-6-\[18F\]fluorodibenzo\[b,d\]thiophene 5,5-dioxide): Brain imaging of alpha-7 nicotinic acetylcholine receptors Contingency Management: Incentive payments contingent upon provision of samples that meet criterion levels of exhaled carbon oxide and urinary cotinine at study visits
Performance on the Paced Serial Addition Task (PASAT) Baseline	65.7 correct responses Standard Deviation 10.5
Performance on the Paced Serial Addition Task (PASAT) PET day	71.7 correct responses Standard Deviation 6.1

Adverse Events

Tobacco Smokers During a Quit Attempt

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Elise Weerts, Professor

Johns Hopkins School of Medicine

Phone: 410-550-2781

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place