Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

NCT03309943 | Completed Phase 4 Results FDA Drug

• 1 other identifier: Pro00083809
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Cigarette Smoking

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Laboratory Visit - Self-Reported Craving

  Lab Task: 2-3 hours post-administration

• Laboratory Visit - # Cigarette Puffs

  Lab Task: 2-3 hours post-administration

Study Arms (2)

Propranolol

EXPERIMENTAL

Propranolol Capsule: 40 mg IR, administered 2x at separate laboratory sessions

Drug: Propranolol

Placebo

PLACEBO COMPARATOR

Placebo Capsule: No active ingredients, administered 2x at separate laboratory sessions

Drug: Placebo

Interventions

Propranolol DRUG

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

Propranolol

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Duke University: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Cigarette Smoking

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

This was a pilot study with a small sample size. A between-subjects design was used with no baseline scan for comparison. No clinical endpoints were examined - results are limited to neuroimaging and behavioral task outcomes.

Results Point of Contact

• Title: Jason A. Oliver, Ph.D.
• Organization: Duke University School of Medicine

Jason.A.Oliver@duke.edu

(919) 668-0093

Study Officials

• Jason A Oliver, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to receive propranolol (40 mg) or placebo

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 16, 2017
• Study Start: January 16, 2018
• Primary Completion: July 15, 2019
• Study Completion: July 15, 2019
• Last Updated: August 13, 2020
• Results First Posted: August 13, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: We anticipate making data available within six months of study completion. It will be available for an indefinite period of time.
• Access Criteria: Contact PI for details

Locations

US (1)