Beta-Adrenergic Modulation of Drug Cue Reactivity

Nicotine Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05587361
• Other study ID #: 2022005-OSU-CHS
• Secondary ID: 1R01DA053342-01A
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: June 1, 2024
• Est. completion date: March 30, 2025

Study information

• Verified date: April 2024
• Source: University of Oklahoma
• Contact: Jason A Oliver, PhD
• Phone: 405-271-8001
• Email: Jason-Oliver[@]ouhsc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: March 30, 2025
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cigarette Smoking
• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Drug:
• Propranolol
Propranolol Capsule; 40 mg IR
• Nicotine Patch
Nicotine Patch; 14 mg
• Placebo Propranolol
Placebo Capsule, no active ingredients
• Placebo Patch
Placebo Patch, no active ingredients

Locations

Country	Name	City	State
United States	Hardesty Center for Clinical Research and Neuroscience	Tulsa	Oklahoma

Sponsors (5)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Approximately 4-5 hours
Primary	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	Approximately 4-5 hours
Primary	Association between Smoking Urge and Brain Activation	Indices of covariation between cue-provoked craving BOLD activation to smoking cues	Approximately 4-5 hours
Primary	Hippocampus-Amygdala connectivity to smoking cues	Index of connectivity between these brain regions	Approximately 4-5 hours
Primary	Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity	Index of connectivity between these brain regions	Approximately 4-5 hours
Primary	Association between Smoking Urge and Brain Connectivity	Indices of covariation between cue-provoked craving BOLD activation to smoking cues	Approximately 4-5 hours