Enhancing Relapse Prevention with rTMS: Dose-Response Parameters for Smoking Cessation

利用 rTMS 加强复发预防：戒烟剂量反应参数

基本信息

批准号：
10405126
负责人：
Christine Elizabeth Sheffer
金额：
$ 47.85万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405126
关键词：
Abstinence Accounting Address Behavioral Biological Models Brain Brain region Cause of Death Cerebrovascular Circulation Cessation of life Clinical Psychology Cognitive Cognitive Therapy Cues Disease Dose Double-Blind Method Equilibrium Evidence based treatment Food Frequencies Goals Impulsivity Lead Left Link Malignant Neoplasms Malignant neoplasm of lung Mediating Methodology Methods Motivation Neurobiology Neurons Neurophysiology - biologic function Neuropsychology Nicotine Outcome Participant Physiologic pulse Prefrontal Cortex Prevalence Psychological reinforcement Public Health Randomized Randomized Controlled Trials Relapse Relative Risks Research Rewards Role Self-control as a personality trait Smoke Smoker Smoking Stimulus System Techniques Time Tobacco Dependence Tobacco use Water addiction behavioral economics cigarette smoking clinical application cognitive function comparison group conditioning design discounting disorder later incidence prevention efficacy testing efficacy trial evidence base executive function improved incentive salience innovation neurobehavioral neurochemistry neuroimaging non-compliance noninvasive brain stimulation prevent relapse risk repetitive transcranial magnetic stimulation response sex side effect skill acquisition smoking cessation success tobacco control uptake

项目摘要

Project Summary / Abstract. Tobacco use remains a significant cause of death and disease. Most smokers want to quit. Over half make a quit attempt every year, but over 90% relapse within 12 months, choosing the immediate reinforcement of smoking over the long-term benefits of quitting. Innovative methods for preventing relapse are needed. The Competing Neurobehavioral Decision Systems (CNDS) model posits that decisions are driven by interactions between the executive function network, located in the prefrontal cortex (PFC); and the impulsive network, located in limbic and paralimbic brain regions. Behavioral economic, neuroimaging, neurobiological, and neurobehavioral studies support this conceptualization. Greater PFC activity is linked with more self-control, more prudent choices, decreased delay discounting rates, and increased abstinence rates. The dorsolateral prefrontal cortex (DLPFC), a functional node in the PFC, has a significant role in executive function network. We propose that increasing activity in the DLPFC will reduce relapse to smoking. High frequency repetitive transcranial magnetic stimulation (rTMS) selectively modulates neuronal activity. In a randomized, double-blind, sham-controlled trial, we found 8 sessions (1/day), active or sham 20Hz rTMS (900 pulses) of the left DLPFC combined with a cognitive-behavioral intervention (CBI) to increase latency to relapse, short-term abstinence rates, and delay discounting The mean/median latency to relapse for active rTMS was n=45.2 and n=33.5 days compared with n=20.5 and n=8 days for sham. Active rTMS reduced the relative risk of relapse 3-fold (RR 0.29, CI 0.10-0.76, p =.01). Active rTMS also increased 12-week abstinence rates (50% vs. 15.4%, p=.05), decreased delay discounting rates, and increased the uptake of the CBI. While this evidence is compelling, an optimal dosing strategy must be determined before a long-term efficacy trial can be conducted. The goal of this project is to determine a dosing strategy for 20Hz rTMS that will produce the best long-term abstinence outcomes with the fewest undesirable effects. We will use a fully crossed, double-blinded, randomized factorial design with three factors: duration (stimulation days: 8, 12, and 16), intensity (900 or 1800 pulses per day), and a sham control for each condition. The sham control will allow for a comparison group to calculate effect sizes and account for non-specific treatment-related effects. Outcomes will include latency to relapse, 12 and 24-week point prevalence abstinence rates, delay discounting rates, cognitive-behavioral skills acquisition, and potential undesirable effects (e.g., non- compliance due to participant burden). Aim One will examine the effects of stimulation duration and intensity on all outcomes among motivated smokers (n=258). Aim Two will identify the most promising dosing strategy by systematically balancing effect sizes and undesirable effects. Establishing a dose-response relationship is critical to developing rTMS as a potential treatment for tobacco dependence. This innovative project will significantly advance research in the clinical application of rTMS in the treatment for tobacco dependence.

项目摘要 /摘要。使用烟草仍然是死亡和疾病的重要原因。大多数吸烟者想退出。每年超过一半的戒烟尝试，但在12个月内复发超过90％，选择立即加强戒烟的长期益处。预防的创新方法需要复发。竞争的神经行为决策系统（CND）模型认为该决策由位于前额叶皮层（PFC）的执行功能网络之间的相互作用驱动；和冲动网络，位于边缘和旁皮大脑区域。行为经济，神经影像，神经生物学和神经行为研究支持这一概念化。较大的PFC活动与更多的自我控制，更谨慎的选择，降低延迟折现率和戒酒率的提高。 PFC中的功能性节点，背外侧前额叶皮层（DLPFC）在执行中具有重要作用功能网络。我们建议，DLPFC的活动增加将减少吸烟的复发。高频重复的经颅磁刺激（RTMS）选择性调节神经元活性。在随机，双盲，假对照试验，我们发现了8个会话（1/天），活动或假20Hz RTM（900 左DLPFC的脉冲）与认知行为干预（CBI）相结合，以增加潜伏期的潜伏期复发，短期禁欲率以及延迟打折的平均/中位潜伏期以复发以复发 RTM为n = 45.2，n = 33.5天，而n = 20.5，而n = 8天。主动rtms降低了复发的相对风险3倍（RR 0.29，CI 0.10-0.76，p = .01）。主动RTM也增加了12周的禁欲利率（50％比15.4％，p = .05），延迟折现率降低，并增加了CBI的吸收。尽管这些证据令人信服，必须在长期疗效试验之前确定最佳剂量策略可以进行。该项目的目的是确定20Hz RTMS的给药策略产生最佳的长期禁欲结果，其不良影响很少。我们将使用完全交叉的，双盲的随机阶乘设计，其中有三个因素：持续时间（刺激天：8、12和16），强度（每天900或1800脉冲），每种条件的假控制。假控制将允许比较组计算效果大小并说明与治疗相关的非特异性治疗效果。结果将包括复发的潜伏期，12点和24周的戒酒率，延迟折现率，认知行为技能的获取以及潜在的不良影响（例如，非 - 由于参与者负担而造成的遵守）。 AIM ONE将检查刺激持续时间和强度的影响在积极吸烟者中的所有结果（n = 258）。目标两个将确定最有希望的给药策略通过系统地平衡效果大小和不良效果。建立剂量反应关系是对于开发RTM作为烟草依赖性的潜在治疗至关重要。这个创新的项目将在RTMS在烟草依赖性治疗中的临床应用中，显着提高了研究。