Sensory Amplifications as Biomarkers of Migraine Progression

感觉放大作为偏头痛进展的生物标志物

• 批准号: 10578609
• 负责人: Kevin Christopher Brennan
• 金额: $ 75.01万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578609
• 关键词: Accounting; Affect; Area; Auditory; Auras; Biological Markers; Brazil; Caring; Chronic; Clinical; Clinical Trials; Data; Development; Diagnosis; Disease; Disease Progression; Disease remission; Distress; Esthesia; Evaluation; Frequencies; Funding; Goals; Headache; Individual; Interview; Machine Learning; Measures; Migraine; Modality; Modeling; Nausea; Neurologic; Pain; Patients; Perception; Performance; Pharmaceutical Preparations; Phase; Phenotype; Phonophobias; Photophobia; Physiological; Physiology; Population; Preventive measure; Prognosis; Psychophysics; Questionnaires; ROC Curve; Reporting; Research; Risk; Risk Factors; Selection for Treatments; Sensory; Severity of illness; Site; Smell Perception; Societies; Statistical Methods; Statistical Models; Symptoms; Testing; Validation; Vertigo; Visual; Work; allodynia; biomarker validation; candidate marker; clinical risk; cohort; comorbidity; cost; disability; disease prognosis; improved; instrument; machine learning method; model development; multimodality; multisensory; nervous system disorder; novel; novel marker; opioid epidemic; opioid overuse; predictive marker; predictive modeling; prevent; preventive intervention; prognostic; prognostic model; prognostic tool; prognostication; response; sensory input; sex; tool

PROJECT SUMMARY/ABSTRACT Migraine affects an estimated 12-15% of the world population. Chronic migraine, which completely disrupts the lives of sufferers, affects close to 3% and accounts for the vast majority of the disability and cost of the disorder. It also contributes to the epidemic of opioid overuse that has been a major impediment to pain care in the past 20 years. One of the highest priorities in migraine research is to understand the progression from episodic to chronic migraine, so it can be prevented. Current clinical criteria are useful for diagnosing episodic and chronic migraine, but they have not necessarily been predictive of progression, and thus are not helpful in identifying subjects at risk.This proposal aims to discover and validate biomarkers of migraine progression. Our key hypothesis is that the sensory amplifications that characterize migraine – photophobia, phonophobia, allodynia, and others – constitute psychophysical and physiological biomarkers, and that they will better predict migraine progression than the current clinically-based gold standard. Our group has shown that different individual sensory amplifications scale with disease severity; our preliminary data shows that their sensitivity is amplified when they are combined. We also propose that though psychophysical/physiological biomarkers are conceptually novel, they are also practical in the clinical setting and indeed consistent with routine neurological evaluation. Our group’s expertise spans the full range of sensory amplifications in migraine and importantly incorporates expertise in developing and validating practical instruments for migraine research and clinical use. The R61 Phase (3 years; 300 high frequency episodic migraineurs followed longitudinally; Aims 1 and 2) will deploy a multimodal, multilevel assessment of sensory amplifications with the goal of identifying the most sensitive measures for prognostication. Aim 1 will provide performance parameters of sensory amplifications as biomarkers of migraine progression. Aim 2 will develop a tool (predictive model) for prognosticating disease progression. This predictive model will explicitly consider sex, aura, and medication use/overuse, as these variables are also well-known to contribute to both sensory amplifications and chronification. Milestones for transition from R61 to R33 will include successful development of a refined battery of sensory tests for formal validation as biomarkers in the R33 Phase. If milestones are met, the R33 Phase (2 years; 100 subjects each in US and Brazil; Aim 3) will validate the refined battery, with the goal of providing optimized tools for use in clinical trials. Thus, Aim 3 will confirm (or refute) the prognostic predictive utility of the model identified in the R61 Phase in two different populations. If successful, this work will deliver the first ever validated prognostic tools to be used in migraine. Their purpose will be to help prevent the progression of episodic to chronic migraine, reduce the attendant opioid overuse that this progression often brings, and ultimately mitigate the overwhelming burden of chronic migraine on patients and society.

项目摘要/摘要 据估计，全世界有12%-15%的人患有偏头痛。慢性偏头痛，它完全扰乱了 患者的生命受到近3%的影响，占该疾病造成的残疾和损失的绝大部分。 它还助长了阿片类药物过度使用的流行，这在过去一直是疼痛护理的主要障碍。 20年了。偏头痛研究的最优先事项之一是了解从发作性到 慢性偏头痛，所以是可以预防的。目前的临床标准对诊断发作性和慢性疾病很有用 偏头痛，但它们不一定能预测病情进展，因此不能帮助识别 高危受试者：该提案旨在发现和验证偏头痛进展的生物标志物。 我们的关键假设是偏头痛的感觉放大--畏光、畏音、 痛觉异常和其他--构成心理物理和生理生物标记物，它们将更好地预测 偏头痛的进展比目前基于临床的黄金标准更好。我们的团队已经证明了不同的 个体感觉放大程度随疾病严重程度而变化；我们的初步数据显示，它们的敏感度是 当它们结合在一起时就放大了。我们还提出，尽管心理物理/生理生物标记物 从概念上来说，它们在临床环境中也是实用的，并且确实与常规神经学相一致 评估。我们团队的专业知识涵盖了偏头痛的所有感觉放大功能，重要的是 整合了开发和验证用于偏头痛研究和临床使用的实用仪器的专业知识。 R61阶段(3年；300名高频发作性偏头痛患者纵向随访；目标1和2)将 部署多模式、多层次的感官放大评估，目标是确定 预测的灵敏措施。目标1将提供感官放大的性能参数如下 偏头痛进展的生物标志物。目标2将开发一种用于预测疾病的工具(预测模型) 进步。这个预测模型将明确考虑性别、气场和药物使用/过度使用，因为这些 众所周知，变量对感觉放大和年代化都有贡献。的里程碑 从R61到R33的过渡将包括成功开发一套完善的感官测试 在R33阶段验证为生物标记物。如果达到里程碑，R33阶段(2年；每100名受试者 美国和巴西；Aim 3)将验证改进后的电池，目标是为临床使用提供优化的工具 审判。因此，目标3将确认(或驳斥)在R61阶段中确定的模型的预测效用 在两个不同的种群中。 如果成功，这项工作将提供第一个用于偏头痛的经过验证的预后工具。他们的目的 将有助于防止发作性偏头痛进展为慢性偏头痛，减少随之而来的阿片类药物过度使用 这种进展通常会给患者带来并最终减轻慢性偏头痛的巨大负担。 和社会。