Neurobehavioral Substrates of Propranolol's Effects on Drug Cue Reactivity
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- BOLD Activation to Smoking Cues - Amygdala
研究概览
简要总结
The central objective of this project is to obtain proof-of-concept data demonstrating the effects of propranolol (a beta-adrenergic antagonist) on neurobiological responses to personal smoking environments and behavioral responses in a laboratory smoking behavior task. Human cigarette smokers (N = 50) will take photographs of locations where they do and do not smoke cigarettes. They will then be randomly assigned to receive either propranolol (40 mg) or placebo prior to completing: A) An MRI session assessing neural responses to personal smoking/non-smoking environments, standard smoking/non-smoking environments and proximal smoking/non-smoking cues; and B) A laboratory session examining smoking behavior in response to environmental cues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between the ages of 18 and 55
- •Generally healthy
- •Right-handed
- •Smoke >= 5 cigarettes/day of a brand delivering 0.5 mg nicotine (FTC method)
- •Have been smoking regularly for >= 1 year, with a stable smoking pattern over the past 6 months
- •Have an expired CO concentration of >= 10 ppm or urinary cotinine > 100 ng/ml
- •Are able to identify at least 4 smoking and 4 non-smoking enviornments
排除标准
- •Inability to attend all required sessions
- •Significant health problems that would interfere with completion of study procedures
- •Presence of conditions that would make MRI unsafe (e.g. pacemaker)
- •Presence of exclusionary psychopathology based on MINI interview (current alcohol/substance use disorder moderate or severe pmild is allowable], any history of bipolar disorder or psychosis). Individuals in early remission from substance use disorder (not in a controlled environment) may also be allowed at the PIs discretion
- •Current use of psychoactive medications per self-report or urine screen. Certain prescribed medications are allowable at the PI's discretion if appropriate documentation (e.g. copy of prescription or physician letter) is provided
- •Positive breath alcohol concentraiton Pregnant, breastfeeding, or planning to become pregnant during the course of study
- •Problems with vision that cannot be corrected with contacts or glasses
- •Current regular use of smokeless tobacco, smoking cessation medications or non-combustible nicotine products (e.g. e-cigarettes)
- •Plans to alter smoking pattern (e.g. reduction, uptake, cessation) during course of study
- •Current use of beta-adrenergic medication
- •Systolic blood pressure < 90 mmHg or diastolic blood pressure < 60 mmHg (sitting or standing)
- •Low resting heart rate (< 60 beats per minute)
- •Abnormal EKG
- •Presence of severe anemia (per complete blood count)
- •Presence of electrolyte imbalance that could impact blood pressure (per metabolic panel)
- •Presence of any other contraindications for propranolol (e.g. cardiovascular disease, bronchial asthma, prior allergic reaction)
- •Note that the above criteria reflect general guidelines for decision-making, but ultimate determinations are left to the discretion of the study physician. Presence of minor (e.g. asymptomatic bradycardia in the range of 50-60 in an otherwise healthy adult) or transient (e.g. electrolyte imbalance readily addressed via changes in fluid intake) may still be deemed eligible to participate.
研究组 & 干预措施
Propranolol
Propranolol Capsule: 40 mg IR, administered 2x at separate laboratory sessions
干预措施: Propranolol (Drug)
Placebo
Placebo Capsule: No active ingredients, administered 2x at separate laboratory sessions
干预措施: Placebo (Drug)
结局指标
主要结局
BOLD Activation to Smoking Cues - Amygdala
时间窗: MRI Scan: 2-3 hours post-administration
BOLD activation in amygdala (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
fMRI BOLD Connectivity
时间窗: MRI Scan: 2-3 hours post-administration
Connectivity with right amygdala when viewing proximal smoking images, using a right anterior hippocampus seed region (psychophysiological interaction analysis; PPI). Larger values represent greater connectivity between these regions while viewing proximal smoking images.
BOLD Activation to Smoking Cues - Anterior Insula
时间窗: MRI Scan: 2-3 hours post-administration
BOLD activation in Anterior Insula (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
BOLD Activation to Smoking Cues - Posterior Hippocampus
时间窗: MRI Scan: 2-3 hours post-administration
BOLD activation in Posterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
BOLD Activation to Smoking Cues - Medial Prefrontal Cortex
时间窗: MRI Scan: 2-3 hours post-administration
BOLD activation in Medial Prefrontal Cortex (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Cue-Provoked Craving - Proximal Cues
时间窗: MRI Scan: 2-3 hours post-administration
During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
BOLD Activation to Smoking Cues - Anterior Hippocampus
时间窗: MRI Scan: 2-3 hours post-administration
BOLD activation in Anterior Hippocampus (% Signal Change). These are analyzed as separate units for each Trial Type (6 total: Proximal Non-Smoking, Proximal Smoking, Standard Environment Non-Smoking, Standard Environment Smoking, Personal Environment Non-Smoking, personal Environment Smoking), MRI Run (4 total: The task was divided into 4 runs to allow for participant breaks) and Brain Hemisphere (2 total: Left and Right). These are only presented by trial type as MRI Run and Brain Hemisphere are not variables of interest.
Cue-Provoked Craving - Standard Environment Images
时间窗: MRI Scan: 2-3 hours post-administration
During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
Cue-Provoked Craving - Personal Environment Cues
时间窗: MRI Scan: 2-3 hours post-administration
During MRI Scans, participants rated their craving in response to the question "While focusing on the place/object, I craved a cigarette." using a 1 (Do not agree) to 8 (Strongly agree) scale immediately following each image. Ratings were then averaged within each image category (total scale range of 1-8). Higher values represent greater craving.
次要结局
- Laboratory Visit - Self-Reported Craving(Lab Task: 2-3 hours post-administration)
- Laboratory Visit - # Cigarette Puffs(Lab Task: 2-3 hours post-administration)