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NCT03309943: ProCue

Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity

Completed Phase 4 Results posted Last updated 13 August 2020
What this trial tests

Phase 4 trial testing Propranolol in Cigarette Smoking in 44 participants. Completed in 15 July 2019.

Timeline
16 January 2018
Primary endpoint
15 July 2019
15 July 2019

Quick facts

Lead sponsorDuke University
PhasePhase 4
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposebasic science
Enrollment44
Start date16 January 2018
Primary completion15 July 2019
Estimated completion15 July 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Duke University

Who can join

Adults 18 to 55, any sex, with Cigarette Smoking. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

BOLD Activation to Smoking Cues - Amygdala Primary · 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.

Non-Smoking Personal Environments
GroupValue95% CI
Propranolol0.002471± 0.367038
Placebo0.077325± 0.337887
Smoking Personal Environments
GroupValue95% CI
Propranolol0.009450± 0.384823
Placebo0.090345± 0.293101
Non-Smoking Standard Environments
GroupValue95% CI
Propranolol0.044903± 0.352711
Placebo0.042836± 0.341324
Smoking Standard Environments
GroupValue95% CI
Propranolol0.111746± 0.321235
Placebo0.161114± 0.355927
Non-Smoking Proximal
GroupValue95% CI
Propranolol0.066409± 0.386921
Placebo0.015171± 0.353829
Smoking Proximal
GroupValue95% CI
Propranolol0.025432± 0.378728
Placebo0.133363± 0.409809
BOLD Activation to Smoking Cues - Anterior Insula Primary · 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.

Non-Smoking Personal Environments
GroupValue95% CI
Propranolol-0.179076± 0.288539
Placebo-0.157851± 0.281748
Smoking Personal Environments
GroupValue95% CI
Propranolol-0.127730± 0.293581
Placebo-0.142636± 0.269551
Non-Smoking Standard Environments
GroupValue95% CI
Propranolol-0.118271± 0.317144
Placebo-0.152299± 0.326875
Smoking Standard Environments
GroupValue95% CI
Propranolol-0.146114± 0.312662
Placebo-0.149887± 0.282468
Non-Smoking Proximal
GroupValue95% CI
Propranolol-0.085715± 0.331652
Placebo-0.085873± 0.270967
Smoking Proximal
GroupValue95% CI
Propranolol-0.086867± 0.352310
Placebo-0.098181± 0.318646
BOLD Activation to Smoking Cues - Anterior Hippocampus Primary · 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.

Non-Smoking Personal Environments
GroupValue95% CI
Propranolol0.061001± 0.324934
Placebo0.095120± 0.271027
Smoking Personal Environments
GroupValue95% CI
Propranolol0.073925± 0.300800
Placebo0.088399± 0.267232
Non-Smoking Standard Environments
GroupValue95% CI
Propranolol0.133369± 0.315323
Placebo0.083638± 0.277520
Smoking Standard Environments
GroupValue95% CI
Propranolol0.171673± 0.289132
Placebo0.186590± 0.300916
Non-Smoking Proximal
GroupValue95% CI
Propranolol0.088852± 0.323655
Placebo0.000827± 0.280219
Smoking Proximal
GroupValue95% CI
Propranolol0.024626± 0.296327
Placebo0.095598± 0.291577
BOLD Activation to Smoking Cues - Posterior Hippocampus Primary · 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.

Non-Smoking Personal Environments
GroupValue95% CI
Propranolol0.161077± 0.288481
Placebo0.185521± 0.262021
Smoking Personal Environments
GroupValue95% CI
Propranolol0.156684± 0.303924
Placebo0.166154± 0.252282
Non-Smoking Standard Environments
GroupValue95% CI
Propranolol0.137124± 0.304769
Placebo0.161655± 0.241679
Smoking Standard Environments
GroupValue95% CI
Propranolol0.179651± 0.256910
Placebo0.176196± 0.269538
Non-Smoking Proximal
GroupValue95% CI
Propranolol0.056247± 0.281092
Placebo0.053026± 0.271871
Smoking Proximal
GroupValue95% CI
Propranolol0.050077± 0.260461
Placebo0.121240± 0.262651
BOLD Activation to Smoking Cues - Medial Prefrontal Cortex Primary · 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.

Non-Smoking Personal Environments
GroupValue95% CI
Propranolol0.033030± 0.322540
Placebo0.012705± 0.409304
Smoking Personal Environments
GroupValue95% CI
Propranolol0.058184± 0.378236
Placebo0.060320± 0.313844
Non-Smoking Standard Environments
GroupValue95% CI
Propranolol-0.078483± 0.350182
Placebo-0.167025± 0.447513
Smoking Standard Environments
GroupValue95% CI
Propranolol-0.068693± 0.311347
Placebo-0.093598± 0.447743
Non-Smoking Proximal
GroupValue95% CI
Propranolol-0.039529± 0.362686
Placebo-0.109172± 0.422732
Smoking Proximal
GroupValue95% CI
Propranolol-0.064034± 0.345958
Placebo0.015524± 0.413311
fMRI BOLD Connectivity Primary · 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.

GroupValue95% CI
Propranolol-0.0740± 0.0769
Placebo0.0228± 0.0997
Cue-Provoked Craving - Proximal Cues Primary · 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.

Non-Smoking
GroupValue95% CI
Propranolol2.866883± 1.566946
Placebo1.898148± 0.824614
Smoking
GroupValue95% CI
Propranolol6.103084± 1.618450
Placebo6.547619± 1.685597
Cue-Provoked Craving - Standard Environment Images Primary · 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.

Non-Smoking
GroupValue95% CI
Propranolol2.673052± 1.681618
Placebo1.763889± 0.644389
Smoking
GroupValue95% CI
Propranolol4.666937± 1.588874
Placebo4.868056± 1.716846
Cue-Provoked Craving - Personal Environment Cues Primary · 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.

Non-Smoking
GroupValue95% CI
Propranolol3.369318± 1.802147
Placebo2.965278± 1.668703
Smoking
GroupValue95% CI
Propranolol6.045996± 1.457661
Placebo6.638889± 1.569405
Laboratory Visit - Self-Reported Craving Secondary · 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 agr

GroupValue95% CI
Propranolol7.3± 2.7
Placebo7.9± 3.0
Laboratory Visit - # Cigarette Puffs Secondary · 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.

GroupValue95% CI
Propranolol15.2± 7.1
Placebo17.7± 9.8

Adverse events — posted to ClinicalTrials.gov

Time frame: This is an acute administration study with an approved medication with a well-established safety profile. Adverse events were assessed over the 1-3 month period in which participants were engaged in the project, primarily for purposes of ensuring new contraindications did not emerge prior to drug administration vs concerns about adverse events related to the drug itself.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Propranolol
Serious: 0/22 (0%)
Deaths: 0/22
Placebo
Serious: 0/22 (0%)
Deaths: 0/22
Other adverse events (2 terms — click to expand)

ReactionSystemPropranololPlacebo
Dog BiteSkin and subcutaneous tissue disorders
Wrist InjuryMusculoskeletal and connective tissue disorders

Data from ClinicalTrials.gov NCT03309943 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Other trials of Propranolol

Trials testing the same drug.

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Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing