Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

Phase 4

Completed

Conditions: Cigarette Smoking

Interventions: Drug: Placebo
Drug: Propranolol

Registration Number: NCT03309943

Lead Sponsor: Duke University

Brief Summary: The central objective of this project is to obtain proof-of-concept data demonstrating the effects of propranolol (a beta-adrenergic antagonist) on neurobiological responses to personal smoking environments and behavioral responses in a laboratory smoking behavior task. Human cigarette smokers (N = 50) will take photographs of locations where they do and do not smoke cigarettes. They will then be randomly assigned to receive either propranolol (40 mg) or placebo prior to completing: A) An MRI session assessing neural responses to personal smoking/non-smoking environments, standard smoking/non-smoking environments and proximal smoking/non-smoking cues; and B) A laboratory session examining smoking behavior in response to environmental cues.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

Inclusion Criteria

Between the ages of 18 and 55
Generally healthy
Right-handed
Smoke >= 5 cigarettes/day of a brand delivering 0.5 mg nicotine (FTC method)
Have been smoking regularly for >= 1 year, with a stable smoking pattern over the past 6 months
Have an expired CO concentration of >= 10 ppm or urinary cotinine > 100 ng/ml
Are able to identify at least 4 smoking and 4 non-smoking enviornments

Exclusion Criteria

Inability to attend all required sessions
Significant health problems that would interfere with completion of study procedures
Presence of conditions that would make MRI unsafe (e.g. pacemaker)
Presence of exclusionary psychopathology based on MINI interview (current alcohol/substance use disorder moderate or severe pmild is allowable], any history of bipolar disorder or psychosis). Individuals in early remission from substance use disorder (not in a controlled environment) may also be allowed at the PIs discretion
Current use of psychoactive medications per self-report or urine screen. Certain prescribed medications are allowable at the PI's discretion if appropriate documentation (e.g. copy of prescription or physician letter) is provided
Positive breath alcohol concentraiton Pregnant, breastfeeding, or planning to become pregnant during the course of study
Problems with vision that cannot be corrected with contacts or glasses
Current regular use of smokeless tobacco, smoking cessation medications or non-combustible nicotine products (e.g. e-cigarettes)
Plans to alter smoking pattern (e.g. reduction, uptake, cessation) during course of study
Current use of beta-adrenergic medication
Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing)
Low resting heart rate (< 60 beats per minute)
Abnormal EKG
Presence of severe anemia (per complete blood count)
Presence of electrolyte imbalance that could impact blood pressure (per metabolic panel)
Presence of any other contraindications for propranolol (e.g. cardiovascular disease, bronchial asthma, prior allergic reaction)

Note that the above criteria reflect general guidelines for decision-making, but ultimate determinations are left to the discretion of the study physician. Presence of minor (e.g. asymptomatic bradycardia in the range of 50-60 in an otherwise healthy adult) or transient (e.g. electrolyte imbalance readily addressed via changes in fluid intake) may still be deemed eligible to participate.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo Capsule: No active ingredients, administered 2x at separate laboratory sessions
Propranolol	Propranolol	Propranolol Capsule: 40 mg IR, administered 2x at separate laboratory sessions

Primary Outcome Measures

Name	Time	Method
BOLD Activation to Smoking Cues - Amygdala	MRI Scan: 2-3 hours post-administration	BOLD activation in amygdala (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
fMRI BOLD Connectivity	MRI Scan: 2-3 hours post-administration	Connectivity with right amygdala when viewing proximal smoking images, using a right anterior hippocampus seed region (psychophysiological interaction analysis; PPI). Larger values represent greater connectivity between these regions while viewing proximal smoking images.
BOLD Activation to Smoking Cues - Anterior Insula	MRI Scan: 2-3 hours post-administration	BOLD activation in Anterior Insula (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
BOLD Activation to Smoking Cues - Posterior Hippocampus	MRI Scan: 2-3 hours post-administration	BOLD activation in Posterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
BOLD Activation to Smoking Cues - Medial Prefrontal Cortex	MRI Scan: 2-3 hours post-administration	BOLD activation in Medial Prefrontal Cortex (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Cue-Provoked Craving - Proximal Cues	MRI Scan: 2-3 hours post-administration	During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
BOLD Activation to Smoking Cues - Anterior Hippocampus	MRI Scan: 2-3 hours post-administration	BOLD activation in Anterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Cue-Provoked Craving - Standard Environment Images	MRI Scan: 2-3 hours post-administration	During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
Cue-Provoked Craving - Personal Environment Cues	MRI Scan: 2-3 hours post-administration	During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.

Secondary Outcome Measures

Name	Time	Method
Laboratory Visit - Self-Reported Craving	Lab Task: 2-3 hours post-administration	Self-reported craving to smoke following presentation of personal smoking environments (prior to ad-lib smoking period). Assessed using the average rating across four questions drawn from the Questionnaire on Smoking Urges: (1) While focusing on those places...nothing would have been better than smoking a cigarette; (2) While focusing on those places...I had the urge for a cigarette; (3) While focusing on those places...all I wanted right then was a cigarette; (4) While focusing on those places...I craved a cigarette. Participants rated each item on an 11-point scale ranging from 0 (Do not agree) to 100 (Strongly agree) in 10-point intervals. These ratings were averaged across items for analysis. higher values represent greater craving. Tiffany, S. T., \& Drobes, D. J. (1991). The development and initial validation of a questionnaire on smoking urges. British Journal of addiction, 86(11), 1467-1476.
Laboratory Visit - # Cigarette Puffs	Lab Task: 2-3 hours post-administration	Number of cigarette puffs taken during ad lib smoking period while participants view images of their personal smoking environment. Smoking was video recorded and puffs were coded by two raters.