Identifying Neurobiological Mechanisms That Underlie Acute Nicotine Withdrawal and Drive Early Relapse in Smokers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Behavioral Reaction Speed on the Parametric Flanker Task
研究概览
简要总结
Background:
- Smoking is thought to cause changes in the brain that lead to addiction and craving. Smokers who try to quit experience nicotine withdrawal symptoms that include irritability, anxiety, and difficulty concentrating. These symptoms make it difficult for people to stop smoking. Many people say that they continue smoking to help relieve these symptoms, often within the first week after trying to quit. Researchers want to study what is happening in the brain to cause these symptoms, which may help identify new ways to successfully quit smoking.
Objectives:
- To study nicotine withdrawal symptoms and brain function in smokers who stop smoking for 36 hours.
Eligibility:
- Individuals between 18 and 65 years of age who smoke at least 10 cigarettes per day. Participants must be able to stop smoking for 36 hours on two occasions.
Design:
Phase 1
- This study will involve three visits to the National Institute on Drug Abuse.
- NOT be able to smoke for 36 hours before the two imaging visits.
- Wear a nicotine skin patch or a placebo (fake) patch during your 36 hour smoking abstinence period and study visits.
- Have your blood drawn to test for levels of stress-related hormones.
- Complete multiple MRI scanning sessions that last about 1.5 to 2 hours each.
- Undergo EEG (brain waves) recording.
- Answer questionnaires about how you think and feel.
- Complete various tasks and procedures inside and outside of the MRI scanner.
Phase 2
- This study will involve thirteen visits to the National Institute on Drug Abuse.
- Set a quit date and develop a treatment plan with a study therapist.
- Take Chantix (varenicline) every day for a period of 12 weeks.
- Meet for weekly and biweekly counseling sessions with a therapist.
- Answer questionnaires about how you think and feel.
Phase 3
- This study will involve three visits to the National Institute on Drug Abuse.
- Complete an MRI scanning session that will last about 20min each visit
- Meet with a study staff member on each visit who will ask you questions about your smoking behavior and how you think and feel.
详细描述
Objective
The primary objective of the current protocol is to gain a greater understanding of the neurobiological mechanisms underlying acute nicotine withdrawal and contributing to the maintenance of, or return to smoking behavior among nicotine-dependent individuals, in the service of developing future smoking cessation treatments. The Nicotine Withdrawal Syndrome is a major cause of failed quit attempts in smokers, and targeting this time period for intervention may help improve smoking cessation outcomes.
Study Population
We will recruit treatment seeking and non-treatment seeking smokers, as well as matched non-smoker control participants.
Design
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
active tDCS
(1) anodal left-dlPFC + cathodal right-vmPFC stimulation, with anode over the left dlPFC and cathode over the right-vmPFC; (2) cathodal left-dlPFC + anodal right-vmPFC stimulation, in which polarity is reversed between the two electrodes
干预措施: Transcranial Direct Current Stimulation (Device)
sham tDCS
To simulate the experience of tDCS stimulation, current is ramped on and turned off at the beginning and end of the tDCS session. An additional sham option is to have the current ramp up and down only at the beginning of the sham session, and not at the end. This second sham is supported in the literature as an effective blinding technique, which subjects cannot distinguish from active stimulation (Gandiga et al 2006, Brunoni et al 2012) . One of these sham options will be used for data that will be analyzed together, to be determined based on equipment capabilities and preliminary analysis of blinding efficacy in our cross over design. We will assess the efficacy of sham condition by providing participants and the investigator with a questionnaire on the MRI/tDCS session, wherein they will report whether they thought the tDCS session was active or sham. The MRI operator (or other non protocol personnel) will control active/sham conditions.
干预措施: sham (Device)
Main Study - Treatment
Healthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits.
Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist.
Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions.
Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session.
干预措施: Nicotine patch (Drug)
Main Study - Treatment
Healthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits.
Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist.
Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions.
Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session.
干预措施: Placebo patch (Drug)
Main Study - Treatment
Healthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits.
Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist.
Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions.
Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session.
干预措施: Varenicline Pill (Drug)
Main Study - Treatment
Healthy male and female adults who smokers are actively seeking treatment for smoking cessation were asked to complete three study phases: pre-treatment study visits, treatment visits and post-treatment follow-up visits.
Pre-treatment (phase 1): 2 MRI sessions: dose-matched nicotine patch or placebo patch during a 36hr smoking abstinence period completed prior to each. Within ~ 2wks of their second scan visit, participants will have 1-3 pre-treatment preparation visits with a therapist.
Treatment (Phase 2): 15-18 visits over ~16-19 weeks. First dose of varenicline (0.5 - 1mg/day), 1 week prior to their quit date followed by 12wks of daily varenicline (2mg/day) as well as weekly and biweekly 30min counseling sessions.
Follow-up Phase 3: visits at 1, 6, and 12 months after their last treatment visit to assess quit status and smoking abstinence since last visit, complete a series of state measures and complete a 15-20 min scan session.
干预措施: Placebo pill (Drug)
Main Study - Non-Treatment
Healthy male and female adults who have a history of 1 or more years of consistently smoking cigarettes with a urine cotinine level corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml, but who are not currently seeking treatment for smoking cessation. Non-treatment seeking smokers will not set a quit date or make a quit attempt, will not complete a treatment program as part of this study and will not be followed up after they complete the two pre-treatment visits.
干预措施: Nicotine patch (Drug)
Main Study - Non-Treatment
Healthy male and female adults who have a history of 1 or more years of consistently smoking cigarettes with a urine cotinine level corresponding to smoker status for the specific test being used, typically corresponding to a urine cotinine above about 200 ng/ml, but who are not currently seeking treatment for smoking cessation. Non-treatment seeking smokers will not set a quit date or make a quit attempt, will not complete a treatment program as part of this study and will not be followed up after they complete the two pre-treatment visits.
干预措施: Placebo patch (Drug)
Main Study - Motivational Interviewing
Current smokers who meet criteria for participation but who are not currently ready to enter treatment for smoking cessation. These subjects will receive motivational interviewing to prepare them for a tobacco cigarette quit attempt.
干预措施: Motivational Interviewing (Behavioral)
结局指标
主要结局
Behavioral Reaction Speed on the Parametric Flanker Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction speed on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Accuracy on the Matching Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Reaction Speed on the Matching Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Reaction speed on the Matching Task. Task consisted of 2 conditions: match faces, where 2 faces appeared at the top of the screen and one at the bottom (target). Participants needed to press a button corresponding to the top row face that matched the target; the control condition was identical, except instead of faces the images consisted of simple shapes (e.g. ovals).Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Nicotine Withdrawal From WSWS
时间窗: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Nicotine withdrawal as measured from the total score on the Wisconsin Smoking Withdrawal Scale (WSWS). The WSWS is a 28-item questionnaire ranging from 0 (strongly disagree) to 4 (strongly agree). The total score ranges from 0 to 112, with higher scores indicating more withdrawal symptoms. Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Nicotine Craving From TCQ-SF
时间窗: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Nicotine craving as measured from the total score on the Tobacco Craving Questionnaire-Short Form (TCQ-SF). The TCQ-SF is a 12-item questionnaire designed to measure craving for cigarettes. Each question is answered on a 7-point scale from 1 (Strongly Disagree) to 7 (Strongly Agree). Total scores range from 12 to 84, with higher scores indicating more craving. Cigarette smokers were 12 hour (overnight) abstinent and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
BOLD Activation in Right ACC During Parametric Flanker Task tDCS Stimulation
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condidtion)
BOLD percent signal change in right Anterior Cingulate Cortex (rACC) during parametric flanker task. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo). The 3 task conditions are congruent (i.e. flanker stimuli are identical to target) and medium and high levels of incongruent.
dACC Glutamate
时间窗: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Glutamate measured in the dorsal Anterior Cingulate Cortex (dACC) measured as a ratio to Creatine and Phosphocreatine. Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
Behavioral Accuracy on N-Back Working Memory Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Reaction Speed on N-Back Working Memory Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on N-Back Working Memory Task. Task consisted of 0-back, 1-back and 3-back. In this task, participants respond with a button when the current stimulus is the same as the previous one (1-back), the one 3 stimuli earlier (3-back) or the letter 'D' (0-back) depending upon task condition. Table values are reaction time speeds. This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Behavioral Accuracy on the Parametric Flanker Task
时间窗: During tDCS or sham stimulation. Day 1 for non-smokers. Day 1 or 2 for smokers (counterbalanced for nicotine condition)
Behavioral Performance on Parametric Flanker Task. Task consisted of 3 levels of difficulty: congruent trials (where distractors are the same as the target; e.g. HHHHHHH), incongruent2 trials (where the 2 furthest distractors on each side were incongruent with the target; e.g. HHSSSHH) and incongruent3 trials (where all distractors are incongruent with the target; e.g. HHHSHHH). Table values are accuracy as a percentage (i.e total times they reponded correctly / total trials). This table is during 2mA Anodal tDCS at the left Dorsolateral prefrontal cortex (dlPFC), 2mA Cathodal tDCS at left dlPFC, or sham stimulation (i.e. placebo).
Affect From PANAS
时间窗: 12 hours nicotine abstinent (plus 1-2 hours after patch)
Positive and Negative mood from the Positive and Negative Affect Schedule (PANAS). The PANAS consists of 20 words related to emotions that participants indicate to what extent they felt this way in the last week. Words are rated from 1 (very slightly or not at all) to 5 (extremely). The PANAS is broken into a Positive and Negative subscale, each consisting of 10 questions and thus ranging from 10 to 50. Higher numbers are indicative of higher levels of positive affect and higher levels of negative affect respectively. Cigarette smokers were 12 hour (overnight) abstinent, and had either a nicotine patch or a placebo patch placed 1-2 hours before scanning.
次要结局
未报告次要终点