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.

烟草使用仍然是美国头号可预防的死亡原因。不幸的是， 精神健康状况受到不成比例的影响。美国退伍军人的烟草使用率也很高， 那些经历过创伤的人更有可能吸烟。成功戒烟对于那些 患有创伤后应激障碍（PTSD）的人。尽管目前的循证医学 在戒烟的药物疗法和心理疗法方面，迫切需要替代疗法。 神经成像技术，如静息态功能性磁共振成像（rs-fMRI）提供了 深入了解烟草使用障碍（TUD）和成功戒烟尝试的神经回路。的干预措施 调节TUD潜在的神经系统，如重复经颅磁刺激（rTMS），可能是 对改善临床结果至关重要。事实上，美国食品和药物管理局（FDA）最近批准了一份表格， rTMS作为成人短期戒烟治疗的研究。然而，大多数针对吸烟的rTMS临床试验 在平民样本中进行了戒烟，并排除了有精神病的个人。到 改善患有PTSD退伍军人的戒烟治疗选择，评估新的大脑至关重要 刺激方法，如rTMS在这个脆弱的人群。此外，神经科学的发展- 基于rs-fMRI的神经导航等增强rTMS的信息技术对rTMS的个体化至关重要 戒烟和了解作用机制。神经影像学在发展中的应用 已经成功应用了个性化rTMS靶点，以精确调节靶向潜在神经回路 重度抑郁症（MDD）的治疗。类似的方法已成功地证明， 戒烟的候选人的导师，但这项工作是在平民参与者的样本完成 没有精神疾病的人试图戒烟。为了填补这些知识空白，拟议的研究 旨在为退伍军人个体化神经导航rTMS的治疗应用开发可行性数据 患有创伤后应激障碍试图戒烟采用可行性随机对照试验（RCT）设计，合格 寻求戒烟的PTSD退伍军人（n=50）将在5天的治疗前后接受rs-fMRI检查， 戒烟前一周接受神经导航rTMS，联合尼古丁替代疗法（NRT）， 认知行为疗法（CBT）这项研究的科学目的是评估治疗的可行性 程序，制定初步的效应量估计，并证明干预的目标参与 对TUD至关重要的神经网络此外，补充培训和辅导计划将提供 接受指导临床研究培训的候选人，支持完成CDA-2研究， 准备一份优秀评审奖申请。具体来说，候选人将发展rTMS的技术熟练程度 治疗和基于fMRI的神经导航，熟练掌握临床试验，培训和临床研究经验 与退伍军人健康相关的领域，包括创伤后应激障碍和戒烟，以及行政，分析和 授予写作技能。建议的研究性学习和培训计划为候选人提供了发展的平台 并实施一项完整的RCT，旨在量化rs-fMRI引导的rTMS戒烟的疗效， 患有创伤后应激障碍的退伍军人最终，这条研究路线将使候选人建立独立性， 医生科学家在退伍军人事务部，并追求事业的发展，非 对患有共病物质使用和精神疾病的退伍军人进行侵入性神经调节治疗。