Clinical trial NCT05587361: Beta-Adrenergic Modulation of Drug Cue Reactivity
Official title: Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Tobacco Use Disorder
Nicotine Dependence
Cigarette Smoking
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: Oklahoma State University Center for Health Sciences
name: Duke University
name: National Institute on Drug Abuse (NIDA)
name: National Institutes of Health (NIH)
First posted: 2022-10-20
Enrollment: 80
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Cue-Provoked Craving Ratings
timeFrame: Approximately 4-5 hours
measure: Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues
timeFrame: Approximately 4-5 hours
measure: Association between Smoking Urge and Brain Activation
timeFrame: Approximately 4-5 hours
measure: Hippocampus-Amygdala connectivity to smoking cues
timeFrame: Approximately 4-5 hours
measure: Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity
timeFrame: Approximately 4-5 hours
measure: Association between Smoking Urge and Brain Connectivity
timeFrame: Approximately 4-5 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Tulsa
country: United States
facility: Hardesty Center for Clinical Research and Neuroscience
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Jason A Oliver, PhD
role: PRINCIPAL_INVESTIGATOR
References: