Neuroimaging correlates and feasibility of transcranial magnetic stimulation (TMS) to improve smoking cessation outcomes in Veterans with comorbid PTSD

神经影像学相关性和经颅磁刺激 (TMS) 改善患有 PTSD 退伍军人戒烟结果的可行性

• 批准号: 10590175
• 负责人: Jonathan R Young
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590175
• 关键词: Abstinence; Adult; Affect; Award; Brain; Carbon Monoxide; Cause of Death; Cessation of life; Chronic; Cigarette; Clinical; Clinical Research; Clinical Trials; Cognitive Therapy; Confidence Intervals; Consumption; Data; Development; Devices; Double-Blind Method; Economics; Eligibility Determination; Enrollment; Ensure; Exclusion; Exhalation; Feasibility Studies; Functional Magnetic Resonance Imaging; General Population; Goals; Grant; Health; Healthcare; Individual; Insula of Reil; Intervention; Knowledge; Life Expectancy; Major Depressive Disorder; Measures; Mental Health; Mental disorders; Mentors; Methodology; Methods; Modality; Neuronavigation; Neurosciences; Outcome; Participant; Pharmacotherapy; Physicians; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Preparation; Procedures; Psychotherapy; Public Health; Randomized; Randomized, Controlled Trials; Research; Research Training; Resistance; Rest; Risk; Sampling; Scientist; Smoke; Smoker; Smoking; Smoking Cessation Intervention; Structure; Structure of postcentral gyrus; Study Section; Substance Use Disorder; System; Techniques; Testing; Therapeutic; Tobacco Use Disorder; Tobacco smoking behavior; Tobacco use; Traction; Training; Training Support; Transcranial magnetic stimulation; Trauma; Uncertainty; United States; United States Department of Veterans Affairs; United States Food and Drug Administration; Veterans; Vulnerable Populations; Work; Writing; acceptability and feasibility; active comparator; alternative treatment; career; clinical efficacy; comorbidity; disability; effective therapy; evidence base; experience; feasibility trial; improved; independent component analysis; innovation; insight; multi-component intervention; multimodality; neural; neural circuit; neural network; neuroimaging; neuroregulation; nicotine replacement; noninvasive brain stimulation; novel; open label; placebo group; poor health outcome; recruit; repetitive transcranial magnetic stimulation; research study; retention rate; skills; smoking abstinence; smoking cessation; smoking initiation; smoking prevalence; substance use; substance use treatment; trauma exposure; treatment effect; trial comparing; trial design

Tobacco use remains the number one preventable cause of death in the United States. Unfortunately, individuals with mental health conditions are disproportionately affected. Tobacco use is also high among US Veterans, and those who have experienced trauma are even more likely to smoke. Successful quitting is especially difficult for individuals who develop posttraumatic stress disorder (PTSD). Despite the efficacy of current evidence-based pharmacotherapies and psychotherapies for smoking cessation, alternative treatments are critically needed. Neuroimaging techniques such as resting-state functional magnetic resonance imaging (rs-fMRI) have provided insight into the neurocircuitry of tobacco use disorder (TUD) and successful quit attempts. Interventions that modulate the neural systems underlying TUD, such as repetitive transcranial magnetic stimulation (rTMS), may be critical to improving clinical outcomes. Indeed, the US Food and Drug Administration (FDA) recently cleared a form of rTMS as a short-term smoking cessation treatment in adults. However, most clinical trials on rTMS for smoking cessation have been conducted in civilian samples and have excluded individuals with psychiatric conditions. To improve smoking cessation treatment options for Veterans with PTSD, it is critical to evaluate novel brain stimulation methods such as rTMS in this vulnerable population. Furthermore, the development of neuroscience- informed techniques to enhance rTMS such as neuronavigation based on rs-fMRI is critical to individualizing rTMS for smoking cessation and understanding mechanisms of action. The application of neuroimaging to develop personalized rTMS targets to precisely modulate targeted underlying neurocircuitry has been successfully applied to the treatment of major depressive disorder (MDD). Similar methodology has been demonstrated successfully for smoking cessation by the candidate’s mentors, but this work was completed in a sample of civilian participants making a quit attempt who did not have psychiatric illness. To fill these knowledge gaps, the proposed research aims to develop feasibility data for the therapeutic application individualized neuronavigated rTMS for Veterans with PTSD attempting to quit smoking. Using a feasibility randomized controlled trial (RCT) design, eligible Veterans with PTSD (n=50) seeking smoking cessation will receive rs-fMRI before and after a 5-day course of neuronavigated rTMS the week prior to their quit date, in conjunction with nicotine replacement therapy (NRT) and cognitive behavioral therapy (CBT). The scientific aims of the study are to evaluate feasibility of treatment delivery procedures, develop preliminary effect size estimates, and demonstrate target engagement of the intervention within neural networks critical to TUD. In addition, complementary training and mentoring plans will provide the candidate with mentored clinical research training that supports the completion of the CDA-2 research study and preparation a Merit Review award application. Specifically, the candidate will develop technical proficiency in rTMS therapy and fMRI-based neuronavigation, proficiency in clinical trials, training, and experience in clinical research domains relevant to Veteran health including PTSD and smoking cessation, and administrative, analytical and grant writing skills. The proposed research study and training plan provide a platform for the candidate to develop and implement a full RCT aimed at quantifying the efficacy of rs-fMRI-guided rTMS for smoking cessation in Veterans with PTSD. Ultimately, this line of research will allow the candidate to establish independence as a physician scientist at the Department of Veterans Affairs and to pursue a career on the development of non- invasive neuromodulation treatments for Veterans with comorbid substance use and psychiatric disorders.

不幸的是，烟草使用了可预防的死亡原因 在心理健康状况下，烟草的使用也很高。 Those Who Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Ho Experience 尽管当前基于证据的人有疗效，但患有创伤后应激障碍的人 需要戒烟的药物治疗和心理治疗，替代治疗是至关重要的。 已经提供了神经影像学技术，例如静止状态功能磁共振成像（RS-FMRI） 干预措施的干预措施 调节TUD基础的神经系统，例如重复的经颅磁刺激（RTMS），可能是Bee 对于改善临床结果至关重要。 RTMS作为成人的Ashort期限戒烟治疗。 在平民样本中采样了精神病学结构 改善PTSD退伍军人的戒烟治疗选择，评估新颖的Braine至关重要 弱势人群中的RTM等刺激方法。 知情的技术来增强基于RS-FMRI的神经元驾驶等RTMS RTMS对于个体化RTMS至关重要 戒烟和理解作用机制。 已成功应用了针对模块化靶向神经通路的个性化RTMS目标 治疗主要抑郁症（MDD）。 候选人的导师戒烟，但是这项工作工作是在平民参与者样本中完成的 戒烟没有精神病来填补知识差距。 旨在为退伍军人的治疗应用个性化的神经宣传的RTMS开发可行数据 使用PTSD戒烟，使用可行性随机对照试验（RCT）设计 PTSD（n = 50）寻求戒烟的退伍军人将在5天的课程之前和之后获得RS-FMRI 神经脱位在退出日期之前的一周与尼古丁替代疗法（NRT）和 认知行为疗法（CBT）。 程序，开发人员，预后估算并证明了干预tiontiontiontiontiontiontion的目标参与 在神经网络中，TUD至关重要。 候选人接受指导的临床研究培训，该培训支持CDA-2研究的压缩和 准备好审查奖的申请。 基于治疗和基于功能磁共振成像的神经元活动，临床试验的熟练程度，培训和临床研究经验 与退伍军人健康相关的领域，包括PTSD和戒烟，以及分析性的分析 授予写作技巧。 并实施旨在量化RS-FMRI引导的RTMS戒烟的功效的完整RCT 具有PTSD的退伍军人。 退伍军人部的医师科学家，并从事非 - 与Comort药物使用和智慧疾病的退伍军人的侵入性神经调节治疗。