Beta-Adrenergic Modulation of Drug Cue Reactivity

• Sponsor: University of Oklahoma (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05587361
• Collaborator: Oklahoma State University Center for Health Sciences (Other), Duke University (Other), National Institute on Drug Abuse (NIDA) (NIH), National Institutes of Health (NIH) (NIH)
• Enrollment: 80
• Location: 1
• Arms: 4
• Anticipated Duration (Months): 36
• Patients Per Site Per Month: 2.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Tobacco Use Disorder; Nicotine Dependence; Cigarette Smoking	Drug: Propranolol; Drug: Nicotine Patch; Drug: Placebo Propranolol; Drug: Placebo Patch	Phase 4

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms
• Anticipated Study Start Date: Nov 1, 2022
• Anticipated Primary Completion Date: Nov 1, 2025
• Anticipated Study Completion Date: Nov 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Patch/Placebo Propranolol Placebo Nicotine Patch Placebo Propranolol	Drug: Placebo Propranolol; Placebo Capsule, no active ingredients; Drug: Placebo Patch; Placebo Patch, no active ingredients
Experimental: Placebo Patch/Active Propranolol Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)	Drug: Propranolol; Propranolol Capsule; 40 mg IR; Drug: Placebo Patch; Placebo Patch, no active ingredients
Experimental: Active Patch/Placebo Propranolol Active Nicotine Patch (14 mg) Placebo Propranolol	Drug: Nicotine Patch; Nicotine Patch; 14 mg; Drug: Placebo Propranolol; Placebo Capsule, no active ingredients
Experimental: Active Patch/Active Propranolol Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)	Drug: Propranolol; Propranolol Capsule; 40 mg IR; Drug: Nicotine Patch; Nicotine Patch; 14 mg

Outcome Measures

Primary Outcome Measures

1. Cue-Provoked Craving Ratings [Approximately 4-5 hours]

   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.

2. Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues [Approximately 4-5 hours]

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

3. Association between Smoking Urge and Brain Activation [Approximately 4-5 hours]

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

4. Hippocampus-Amygdala connectivity to smoking cues [Approximately 4-5 hours]

   Index of connectivity between these brain regions

5. Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity [Approximately 4-5 hours]

   Index of connectivity between these brain regions

6. Association between Smoking Urge and Brain Connectivity [Approximately 4-5 hours]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Generally healthy

2. Age 21-60

3. Right-handed using a three-item scale

4. Daily smoker of ≥ 5 cigarettes/day delivering 0.5 mg nicotine (FTC)

5. Smoking regularly for ≥ 1 year, with stable smoking for the past 6 months

6. Afternoon expired Carbon Monoxide (CO) concentration ≥ 6 ppm and/or morning urinary cotinine >100 ng/ml

7. Must identity at least 4 different smoking locations used in a typical week

8. Able to read and understand English

Exclusion Criteria:

1. Inability to attend all required sessions

2. Significant health problems that would preclude active participation

3. Presence of conditions that would make MRI unsafe (e.g. pacemaker) or (e.g. weight and body shape)

4. Current use of psychoactive medications/drugs as indicated by self-report or urine screen

5. Positive breath alcohol concentration

6. Pregnant, breastfeeding, or planning to become pregnant during the course of the study (females)

7. Problems with vision that cannot be corrected with contacts or glasses

8. Current regular use of smokeless tobacco, smoking cessation medications, or other nicotine containing products (e.g. electronic cigarettes)

9. Current use of beta-adrenergic medications (e.g. beta-blockers) or other blood pressure medications

10. Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing)

11. Abnormal EKG

12. Presence of severe anemia

13. Presence of electrolyte imbalance that could impact blood pressure

14. Presence of any other contraindications for propranolol or nicotine patch (e.g. cardiovascular disease, bronchial asthma, prior allergic reactions, diabetes)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hardesty Center for Clinical Research and Neuroscience	Tulsa	Oklahoma	United States	74136

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT05587361
• Other Study ID Numbers: 2022005-OSU-CHS
• First Posted: Oct 20, 2022
• Last Update Posted: Oct 20, 2022
• Last Verified: Oct 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Tobacco Use Disorder; Propranolol; Nicotine

Study Results

No Results Posted as of Oct 20, 2022