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Completed

NCT Number: NCT03309943

Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

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.

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Key information

Conditions

Cigarette Smoking Behavior Smoking Tobacco Smoking Tobacco Use

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Propranolol

Drug

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

Placebo

Drug

Participants will take one dose of Placebo on two separate occasions.

Primary outcomes

  1. BOLD Activation to Smoking Cues - Amygdala

    Time frame: 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.

  2. BOLD Activation to Smoking Cues - Anterior Insula

    Time frame: 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.

  3. BOLD Activation to Smoking Cues - Anterior Hippocampus

    Time frame: 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.

  4. BOLD Activation to Smoking Cues - Posterior Hippocampus

    Time frame: 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.

  5. BOLD Activation to Smoking Cues - Medial Prefrontal Cortex

    Time frame: 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.

  6. fMRI BOLD Connectivity

    Time frame: 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.

  7. Cue-Provoked Craving - Proximal Cues

    Time frame: 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.

  8. Cue-Provoked Craving - Standard Environment Images

    Time frame: 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.

  9. Cue-Provoked Craving - Personal Environment Cues

    Time frame: 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 outcomes

  1. Laboratory Visit - Self-Reported Craving

    Time frame: 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.

  2. Laboratory Visit - # Cigarette Puffs

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)
  • National Institutes of Health (NIH)

Registry information

Acronym: ProCue

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Oct 16, 2017
Registry last updated
Aug 13, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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