Beta-Adrenergic Modulation of Drug Cue Reactivity

University of Oklahoma (OU)

Status and phase: Enrolling; Phase 4

Conditions: Cigarette Smoking; Nicotine Dependence; Tobacco Use Disorder

Treatments: Drug: Placebo Propranolol; Drug: Placebo Patch; Drug: Nicotine Patch; Drug: Propranolol

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05587361

2022005-OSU-CHS

1R01DA053342-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 21 to 60 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

80 participants in 4 patient groups, including a placebo group

Placebo Patch/Placebo Propranolol

Placebo Comparator group

Description:

Placebo Nicotine Patch Placebo Propranolol

Treatment:

Drug: Placebo Patch

Drug: Placebo Propranolol

Placebo Patch/Active Propranolol

Experimental group

Description:

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

Treatment:

Drug: Propranolol

Drug: Placebo Patch

Active Patch/Placebo Propranolol

Experimental group

Description:

Active Nicotine Patch (14 mg) Placebo Propranolol

Treatment:

Drug: Nicotine Patch

Drug: Placebo Propranolol

Active Patch/Active Propranolol

Experimental group

Description:

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

Treatment:

Drug: Propranolol

Drug: Nicotine Patch