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.

项目总结/摘要 偏头痛影响估计12-15%的世界人口。慢性偏头痛，完全扰乱了 患者的生命，影响近3%，占残疾和疾病费用的绝大多数。 它还导致阿片类药物过度使用的流行，这是过去疼痛护理的主要障碍 20年偏头痛研究的最高优先事项之一是了解从发作性到发作性的进展。 慢性偏头痛，所以可以预防。目前的临床标准是有用的诊断发作性和慢性 偏头痛，但他们不一定是预测的进展，因此是没有帮助的识别 该提案旨在发现和验证偏头痛进展的生物标志物。 我们的主要假设是偏头痛的特征性感觉放大-恐惧症，声音恐惧症， 异常性疼痛和其他-构成心理物理和生理生物标志物，并且它们将更好地预测 偏头痛的进展比目前的临床为基础的黄金标准。我们的研究表明， 个体感觉放大与疾病严重程度成比例;我们的初步数据显示， 当它们结合在一起时，我们还提出，虽然心理物理/生理生物标志物是 概念新颖，在临床环境中也很实用，确实与常规神经病学研究一致。 评价我们小组的专业知识涵盖偏头痛的感觉放大的全方位，重要的是， 结合了开发和验证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例高频发作性偏头痛患者纵向随访;目标1和2）将 部署一个多模式，多层次的评估感官放大的目标，以确定最 敏感的测量方法。目标1将提供感官放大的性能参数， 偏头痛进展的生物标志物。目标2将开发一种工具（预测模型）， 进展该预测模型将明确考虑性别、先兆和药物使用/过度使用，因为这些因素 众所周知，变量有助于感觉放大和计时。里程碑 从R61到R33的过渡将包括成功开发一套精致的感官测试， 在R33阶段作为生物标志物进行验证。如果达到里程碑，则R33期（2年;各100例受试者， 美国和巴西;目标3）将验证改进的电池，目标是提供用于临床的优化工具 审判因此，目标3将确认（或反驳）R61阶段中确定的模型的预后预测效用 在两个不同的人群中。 如果成功的话，这项工作将提供第一个被验证的用于偏头痛的预测工具。他们的目的 将有助于预防发作性偏头痛向慢性偏头痛的进展，减少伴随的阿片类药物过度使用， 这一进展常常带来并最终减轻慢性偏头痛对患者的巨大负担 和社会