Beta-Adrenergic Modulation of Drug Cue Reactivity: Neural and Behavioral Mechanisms
概览
- 阶段
- 4 期
- 干预措施
- Propranolol
- 疾病 / 适应症
- Tobacco Use Disorder
- 发起方
- University of Oklahoma
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues
- 状态
- 招募中
- 最后更新
- 4天前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •Generally healthy
- •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
排除标准
- •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)
研究组 & 干预措施
Placebo Patch/Active Propranolol
Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)
干预措施: Propranolol
Active Patch/Active Propranolol
Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)
干预措施: Propranolol
Active Patch/Active Propranolol
Active Nicotine Patch (14 mg) Active Propranolol (40 mg, immediate release)
干预措施: Nicotine Patch
Placebo Patch/Placebo Propranolol
Placebo Nicotine Patch Placebo Propranolol
干预措施: Placebo Propranolol
Placebo Patch/Placebo Propranolol
Placebo Nicotine Patch Placebo Propranolol
干预措施: Placebo Patch
Placebo Patch/Active Propranolol
Placebo Nicotine Patch Active Propranolol (40 mg, immediate release)
干预措施: Placebo Patch
Active Patch/Placebo Propranolol
Active Nicotine Patch (14 mg) Placebo Propranolol
干预措施: Nicotine Patch
Active Patch/Placebo Propranolol
Active Nicotine Patch (14 mg) Placebo Propranolol
干预措施: Placebo Propranolol
结局指标
主要结局
Blood-Oxygen Level Dependent (BOLD) Activation to Smoking Cues
时间窗: 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
Association between Smoking Urge and Brain Activation
时间窗: Approximately 4-5 hours
Indices of covariation between cue-provoked craving BOLD activation to smoking cues
Cue-Provoked Craving Ratings
时间窗: 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.
Hippocampus-Amygdala connectivity to smoking cues
时间窗: Approximately 4-5 hours
Index of connectivity between these brain regions
Medial Prefrontal Cortex and Posterior Cingulate Cortex connectivity
时间窗: Approximately 4-5 hours
Index of connectivity between these brain regions
Association between Smoking Urge and Brain Connectivity
时间窗: Approximately 4-5 hours
Indices of covariation between cue-provoked craving BOLD activation to smoking cues