Towards treatment for the complex patient: investigations of low-intensity focused ultrasound.

针对复杂患者的治疗：低强度聚焦超声的研究。

基本信息

批准号：
10775216
负责人：
MARY LEE
金额：
$ 77.88万
依托单位：
INSTITUTE FOR CLINICAL RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10775216
关键词：
Adverse event Anterior Anxiety Anxiety Disorders Attenuated Behavior Behavioral Brain Brain region Clinical Clinical Research Clinical Treatment Combined Modality Therapy Communities Complex Cues Data Decision Making Disease District of Columbia Dose Double-Blind Method Down-Regulation Emotional Equilibrium Evoked Potentials Focused Ultrasound Generalized Anxiety Disorder Government Hour Hyperactivity Individual Insula of Reil Interoception Investigation Laboratories Location Longevity MRI Scans Measures Mediating Mental disorders Methods Motivation Neurobiology Neuropsychology Opioid Outcome Outcome Measure Pain Pain Disorder Pain Threshold Pain intensity Patients Penetration Phase Physiological Physiological Processes Physiology Population Post-Traumatic Stress Disorders Process Protocols documentation Regulation Role Safety Sampling Signal Transduction Site Social Anxiety Disorder Specificity Structure Symptoms Techniques Transcranial magnetic stimulation Treatment Efficacy Treatment outcome Veterans addiction anxiety states anxiety symptoms biological adaptation to stress brain dysfunction brain magnetic resonance imaging central sensitization chronic back pain chronic pain clinical examination comorbidity conditioned pain modulation cranium craving efficacy evaluation healthy volunteer heart rate variability high risk improved innovation millimeter neurobehavioral neurobiological mechanism neuroregulation novel opioid overdose opioid use disorder overdose death pain processing pain score pain symptom patient population persistent symptom programs recruit reduce symptoms repaired research clinical testing response reward processing safety assessment sensory stimulus sham-controlled study symptomatology therapeutic target

项目摘要

Opioid use disorder with co-morbid chronic pain and anxiety (OCpA) is a clinical triad associated with the highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a complex patient population such as OCpA. In the UG3 phase of this study, we will administer one session of inhibitory LIFU to the AI in individuals with OCpA [opiate use disorder, chronic back pain, and anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)]. The aim of this phase of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. We will also gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and conditioned pain modulation. In the second phase of this project (UH3), we will examine the efficacy, in a larger sample of individuals with OCpA, of repeated LIFU delivery on measures of pain and opiate cue-induced craving, anxiety symptoms, interoception and autonomic reactivity as these outcomes are dysregulated in OCpA and are mediated by the AI. LIFU will be delivered for 10 minutes each hour for 4 hours on a single day. We hypothesize that repeated sessions of LIFU will reduce measures of CS, opiate cue-induced craving, state anxiety symptoms, increase heart rate variability and normalize measures of interoception. We will examine the durability and effect of 1 vs 2 sessions of repeated LIFU on these outcome measures. Repeated sessions of other forms of neuromodulation result in increased magnitude and longer lasting effects. We hypothesize that 2 sessions vs 1 of repeated LIFU will result in greater magnitude of change in the outcome measures. Lastly, we will examine the safety and tolerability of repeated LIFU sessions. There is a need for improved treatments for complex patients such as OCpA beyond combining treatments for each disorder. LIFU provides an ability to transiently and selectively inhibit AI to determine its causal role in OCpA symptoms which then may lead to improved treatments for this clinical triad which is associated with poor treatment outcomes.

阿片类药物使用障碍患有慢性慢性疼痛和焦虑（OCPA）是与临床三合会有关的鸦片过量死亡的最高风险。这三种疾病的同时出现会放大每种症状并导致治疗结果较差。这些疾病有共同的神经生物学基质例如奖励处理和压力响应。前绝缘（AI）是与这些有关的大脑区域过程以及疼痛，成瘾和焦虑的临床障碍。 AI痛苦中的上调，成瘾和焦虑症，因此是神经调节的潜在治疗靶点。低强度集中超声（LIFU）是抑制皮质和深脑区域的无创方法。 Lifu可以深入与传统的非侵入性神经调节方法不同，大脑区域（例如具有空间特异性的AI）缺乏空间特异性和深度渗透。 Lifu可以选择性地针对绝缘区及其子区域并提供了一种潜在的变革性方法来减轻疼痛，鸦片渴望和焦虑的症状复杂的患者人群，例如OCPA。在本研究的UG3阶段，我们将管理一个 OCPA患者的AI抑制性LIFU [鸦片使用障碍，慢性背痛和焦虑症（普遍焦虑症，创伤后应激障碍或社交焦虑症）]。这个阶段的目的这项研究的是确定Lifu vs sham Lifu to ai是安全且耐受性良好的，如不良事件，临床评估和重复的结构性大脑磁共振成像扫描。我们也会收集有关Lifu对AI对阿片类鸦片提示引起的渴望和实验室措施的初步数据中央敏化（CS）发生在疼痛慢性的情况下，例如疼痛和疼痛和条件疼痛调节。在该项目的第二阶段（UH3），我们将在较大的 OCPA的个体样本，重复的LIFU输送在疼痛的度量和阿片类药物诱导的测量中渴望，焦虑症状，互感和自主反应性，因为这些结果在 OCPA，由AI介导。 LIFU将在一天中每小时交付10分钟，持续4小时。我们假设重复的LIFU会议将减少CS的措施，阿片类鸦片提示引起的渴望，状态焦虑症状，增加心率的变异性并使其受感受的措施正常化。我们将检查 1 vs 2会议对这些结果指标的持久性和效果。重复会议其他形式的神经调节导致幅度增加和持久效应。我们假设重复LIFU的2节与1节将导致结果指标的变化更大。最后，我们将研究重复的LIFU会话的安全性和耐受性。需要改进复杂患者的治疗，例如OCPA，除了结合每种疾病的治疗方法之外。 Lifu提供能够瞬时和选择性地抑制AI来确定其在OCPA症状中的因果作用的能力，然后可能会改善该临床三合会的治疗方法，这与不良的治疗结果有关。