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Beta-Adrenergic Modulation of Drug Cue Reactivity

Primary Purpose

Tobacco Use Disorder, Nicotine Dependence, Cigarette Smoking

Status

Not yet recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Propranolol

Nicotine Patch

Placebo Propranolol

Placebo Patch

About this trial

This is an interventional basic science trial for Tobacco Use Disorder

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Generally healthy
Age 21-60
Right-handed using a three-item scale
Daily smoker of ≥ 5 cigarettes/day delivering 0.5 mg nicotine (FTC)
Smoking regularly for ≥ 1 year, with stable smoking for the past 6 months
Afternoon expired Carbon Monoxide (CO) concentration ≥ 6 ppm and/or morning urinary cotinine >100 ng/ml
Must identity at least 4 different smoking locations used in a typical week
Able to read and understand English

Exclusion Criteria:

Inability to attend all required sessions
Significant health problems that would preclude active participation
Presence of conditions that would make MRI unsafe (e.g. pacemaker) or (e.g. weight and body shape)
Current use of psychoactive medications/drugs as indicated by self-report or urine screen
Positive breath alcohol concentration
Pregnant, breastfeeding, or planning to become pregnant during the course of the study (females)
Problems with vision that cannot be corrected with contacts or glasses
Current regular use of smokeless tobacco, smoking cessation medications, or other nicotine containing products (e.g. electronic cigarettes)
Current use of beta-adrenergic medications (e.g. beta-blockers) or other blood pressure medications
Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing)
Abnormal EKG
Presence of severe anemia
Presence of electrolyte imbalance that could impact blood pressure
Presence of any other contraindications for propranolol or nicotine patch (e.g. cardiovascular disease, bronchial asthma, prior allergic reactions, diabetes)

Sites / Locations

Hardesty Center for Clinical Research and Neuroscience

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo Patch/Placebo Propranolol

Placebo Patch/Active Propranolol

Active Patch/Placebo Propranolol

Active Patch/Active Propranolol

Arm Description

Placebo Nicotine Patch Placebo Propranolol

Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)

Active Nicotine Patch (14 mg) Placebo Propranolol

Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)

Outcomes

Primary Outcome Measures

Cue-Provoked Craving Ratings

Self-reported smoking urges in response to smoking and non-smoking cues during magnetic resonance imaging (MRI) scan. Scores range from 0 to 10 with higher values indicating increased craving for cigarettes.

Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues

Blood-Oxygen Level Dependent (BOLD) Contrast (Smoking-Neutral) in Anterior Hippocampus, Amygdala, Dorsal Anterior Insula, Medial Prefrontal Cortex, Posterior Cingulate Cortex and Ventral Striatum

Association between Smoking Urge and Brain Activation

Indices of covariation between cue-provoked craving BOLD activation to smoking cues

Hippocampus-Amygdala connectivity to smoking cues

Index of connectivity between these brain regions

Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity

Index of connectivity between these brain regions

Association between Smoking Urge and Brain Connectivity

Indices of covariation between cue-provoked craving BOLD activation to smoking cues

Secondary Outcome Measures

Full Information

NCT ID

NCT05587361

First Posted

October 3, 2022

Last Updated

April 21, 2023

Sponsor

University of Oklahoma

Collaborators

Oklahoma State University Center for Health Sciences, Duke University, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

1. Study Identification

Unique Protocol Identification Number

NCT05587361

Brief Title

Beta-Adrenergic Modulation of Drug Cue Reactivity

Official Title

Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

June 15, 2023 (Anticipated)

Primary Completion Date

November 1, 2025 (Anticipated)

Study Completion Date

November 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Oklahoma

Collaborators

Oklahoma State University Center for Health Sciences, Duke University, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

This study is designed to investigate the effects of a beta-adrenergic antagonist (Propranolol; 40 mg IR) and nicotine patch (14 mg) administered alone and in combination on neurobiological and behavioral responses to smoking cues in ongoing cigarette smokers. This is a basic experimental study in humans and participants will not take these medications for an extended period or make a cessation attempt as part of their involvement in this research project.

Detailed Description

Cigarette use remains a serious public health problem in the United States and worldwide. Effective pharmacological interventions for smoking cessation exist, but these medications primarily target nicotine withdrawal and smoking reinforcement. The cues and contexts associated with smoking also play an important role in driving smoking behavior, but evidence is extremely mixed whether existing interventions can effectively attenuate smoking urges and behavior in response to these cues and contexts. In a previous pilot trial, the investigators demonstrated that propranolol suppressed smoking cue reactivity and brain activation across a constellation of brain regions implicated in nicotine dependence. Here, the investigators seek to extend this work by examining effects when the drug is administered in combination with an established treatment targeting withdrawal and reinforcement (i.e., nicotine patch). Following consent and screening/baseline activities, participants will attend four neuroimaging appointments each lasting approximately 5 hours. Participants will be fitted with a nicotine or placebo patch, fed a standard meal and then administered propranolol or placebo. Participants will complete questionnaires and have their heart rate/blood pressure monitored throughout the visit. During the MRI scan, participants will be asked to complete both resting scans and task-based scans during which participants will view images of smoking and non-smoking objects and scenes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tobacco Use Disorder, Nicotine Dependence, Cigarette Smoking

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo Patch/Placebo Propranolol

Arm Type

Placebo Comparator

Arm Description

Placebo Nicotine Patch Placebo Propranolol

Arm Title

Placebo Patch/Active Propranolol

Arm Type

Experimental

Arm Description

Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)

Arm Title

Active Patch/Placebo Propranolol

Arm Type

Experimental

Arm Description

Active Nicotine Patch (14 mg) Placebo Propranolol

Arm Title

Active Patch/Active Propranolol

Arm Type

Experimental

Arm Description

Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)

Intervention Type

Drug

Intervention Name(s)

Propranolol

Intervention Description

Propranolol Capsule; 40 mg IR

Intervention Type

Drug

Intervention Name(s)

Nicotine Patch

Intervention Description

Nicotine Patch; 14 mg

Intervention Type

Drug

Intervention Name(s)

Placebo Propranolol

Intervention Description

Placebo Capsule, no active ingredients

Intervention Type

Drug

Intervention Name(s)

Placebo Patch

Intervention Description

Placebo Patch, no active ingredients

Primary Outcome Measure Information:

Title

Cue-Provoked Craving Ratings

Description

Time Frame

Approximately 4-5 hours

Title

Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues

Description

Blood-Oxygen Level Dependent (BOLD) Contrast (Smoking-Neutral) in Anterior Hippocampus, Amygdala, Dorsal Anterior Insula, Medial Prefrontal Cortex, Posterior Cingulate Cortex and Ventral Striatum

Time Frame

Approximately 4-5 hours

Title

Association between Smoking Urge and Brain Activation

Description

Indices of covariation between cue-provoked craving BOLD activation to smoking cues

Time Frame

Approximately 4-5 hours

Title

Hippocampus-Amygdala connectivity to smoking cues

Description

Index of connectivity between these brain regions

Time Frame

Approximately 4-5 hours

Title

Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity

Description

Index of connectivity between these brain regions

Time Frame

Approximately 4-5 hours

Title

Association between Smoking Urge and Brain Connectivity

Description

Indices of covariation between cue-provoked craving BOLD activation to smoking cues

Time Frame

Approximately 4-5 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Generally healthy Age 21-60 Right-handed using a three-item scale Daily smoker of ≥ 5 cigarettes/day delivering 0.5 mg nicotine (FTC) Smoking regularly for ≥ 1 year, with stable smoking for the past 6 months Afternoon expired Carbon Monoxide (CO) concentration ≥ 6 ppm and/or morning urinary cotinine >100 ng/ml Must identity at least 4 different smoking locations used in a typical week Able to read and understand English Exclusion Criteria: Inability to attend all required sessions Significant health problems that would preclude active participation Presence of conditions that would make MRI unsafe (e.g. pacemaker) or (e.g. weight and body shape) Current use of psychoactive medications/drugs as indicated by self-report or urine screen Positive breath alcohol concentration Pregnant, breastfeeding, or planning to become pregnant during the course of the study (females) Problems with vision that cannot be corrected with contacts or glasses Current regular use of smokeless tobacco, smoking cessation medications, or other nicotine containing products (e.g. electronic cigarettes) Current use of beta-adrenergic medications (e.g. beta-blockers) or other blood pressure medications Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing) Abnormal EKG Presence of severe anemia Presence of electrolyte imbalance that could impact blood pressure Presence of any other contraindications for propranolol or nicotine patch (e.g. cardiovascular disease, bronchial asthma, prior allergic reactions, diabetes)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jason A Oliver, PhD

Phone

405-271-8001

Ext

14005

Jason-Oliver@ouhsc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Taylor A Love, BA

Phone

405-746-1799

Taylor-Love@ouhsc.edu

Facility Information:

Facility Name

Hardesty Center for Clinical Research and Neuroscience

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74136

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ashton Baltazar, M.S.

Ashton-Baltazar@ouhsc.edu

First Name & Middle Initial & Last Name & Degree

Taylor A Love, B.A.

Taylor-Love@ouhsc.edu

12. IPD Sharing Statement

Learn more about this trial

Beta-Adrenergic Modulation of Drug Cue Reactivity

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