Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

Cigarette Smoking Clinical Trial

— ProCue  

Official title:

Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03309943
• Other study ID #: Pro00083809
• Status: Completed
• Phase: Phase 4
• Start date: January 16, 2018
• Est. completion date: July 15, 2019

Study information

• Verified date: July 2020
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 15, 2019
• Est. primary completion date: July 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cigarette Smoking

Intervention

Drug:
• Propranolol
Participants will take one dose of Propranolol (40mg IR) on two separate occasions.
• Placebo
Participants will take one dose of Placebo on two separate occasions.

Locations

Country	Name	City	State
United States	Duke University School of Medicine	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BOLD Activation to Smoking Cues - Amygdala	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.	MRI Scan: 2-3 hours post-administration
Primary	BOLD Activation to Smoking Cues - Anterior Insula	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.	MRI Scan: 2-3 hours post-administration
Primary	BOLD Activation to Smoking Cues - Anterior Hippocampus	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.	MRI Scan: 2-3 hours post-administration
Primary	BOLD Activation to Smoking Cues - Posterior Hippocampus	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.	MRI Scan: 2-3 hours post-administration
Primary	BOLD Activation to Smoking Cues - Medial Prefrontal Cortex	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.	MRI Scan: 2-3 hours post-administration
Primary	fMRI BOLD Connectivity	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.	MRI Scan: 2-3 hours post-administration
Primary	Cue-Provoked Craving - Proximal Cues	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.	MRI Scan: 2-3 hours post-administration
Primary	Cue-Provoked Craving - Standard Environment Images	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.	MRI Scan: 2-3 hours post-administration
Primary	Cue-Provoked Craving - Personal Environment Cues	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.	MRI Scan: 2-3 hours post-administration
Secondary	Laboratory Visit - Self-Reported Craving	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.	Lab Task: 2-3 hours post-administration
Secondary	Laboratory Visit - # Cigarette Puffs	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.	Lab Task: 2-3 hours post-administration