Developing Radiocaine NaV imaging as a response monitoring biomarker for chronic pain

开发放射性卡因 NaV 成像作为慢性疼痛的反应监测生物标志物

基本信息

批准号：
10794862
负责人：
Mohab M Ibrahim
金额：
$ 110.6万
依托单位：
LUTROO IMAGING LLC
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：
2023-09-21 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10794862
关键词：
Absence of pain sensation Acute Address Adult Affect Analgesics Anatomy Animal Model Biodistribution Biological Assay Biological Markers Caring Chronic low back pain Clinical Clinical Trials Dangerousness Data Decision Making Development Dexamethasone Dose Drug Kinetics Economic Burden Evaluation Fluorine Goals Healthcare Hour Human Image Imaging Techniques Individual Injections Intravenous Lidocaine Ligands Local Anesthetics Location Low Back Pain Magnetic Resonance Imaging Measurement Measures Methodology Monitor Nature Nerve Nerve Block Neurologic Opioid Pain Pain Measurement Pain intensity Pain management Patient Self-Report Patients Persistent pain Phase I Clinical Trials Phase II Clinical Trials Population Positioning Attribute Positron-Emission Tomography Publishing Reporting Research Resort Resources Rodent Model Roentgen Rays Safety Sample Size Scanning Severities Signal Transduction Sodium Channel Source Technology Testing Therapeutic Time Toxic effect Validation X-Ray Computed Tomography chronic pain chronic pain management clinical practice cohort cost dosimetry experience first-in-human human subject imaging agent imaging biomarker ineffective therapies innovation molecular imaging non-invasive monitor non-opioid analgesic novel opioid epidemic pain behavior pain reduction pain relief pain score pain signal painful neuropathy pre-clinical preclinical safety preclinical toxicity radiotracer response source localization standard care standard of care success therapeutic candidate therapy development tool transmission process treatment effect treatment response uptake voltage

项目摘要

Summary/Abstract There are currently no biomarkers or tools capable of objectively measuring pain signals. Historically, pain in humans has been measured using subjective rating scales to determine its presence and severity. In animal models, pain is measured by semi-quantitative assays that rely on the observation of pain behaviors. Though useful, the inherently subjective nature of these measures has hampered both research and treatment efforts. The annual economic burden of chronic pain is estimated to exceed $800 billion in the USA alone, largely because inadequately managed pain requires disproportionately more healthcare resources. Similarly, clinical trials for pain therapies are the most expensive, and have the lowest success rate, of all neurological indications. Difficulty managing chronic pain has led to the opioid epidemic as many individuals turn to prescription painkillers as a means of relief, but often end up becoming addicted and resorting to more potent and dangerous opioids as their tolerance increases. Radiocaine is a novel positron emission tomography (PET) imaging agent that we are developing as a biomarker to address the issues in pain care and therapy development. Our recently published findings in a rodent model of neuropathic pain demonstrate the ability to localize the pain generator rapidly and accurately and objectively measure its signal intensity. Our ultimate goals are: 1) to change the evaluation of (experimental) pain therapies, and 2) the standard of care in pain assessment through molecular imaging. The use of pain imaging biomarker technology would allow for objective efficacy data (both pre-clinically and in clinical trials), and reduce costs by enabling smaller sample sizes due to more homogeneous populations, i.e. with a particular “pain signal,” and more accurate measurement of analgesic effects. The proposed study will evaluate Radiocaine in early-stage clinical trials. Successful results will set the stage for applied clinical trials that further develop this promising approach into a useful biomarker for transforming pain care.

摘要/摘要目前没有能够明显测量疼痛信号的生物标志物或工具。从历史上看，痛苦人类已使用主观评分量表来确定其存在和严重程度。在动物中模型，疼痛是通过依赖于观察到疼痛行为的半定量测定法来衡量的。尽管这些措施的固有主观性质有用，妨碍了研究和治疗工作。仅在美国，慢性疼痛的年度经济燃烧估计将超过8000亿美元因为管理不足的疼痛需要不成比例的医疗保健资源。同样，临床疼痛疗法的试验是所有神经系统迹象中最昂贵的，并且成功率最低。管理慢性疼痛的困难导致了OOID的流行，因为许多人转向处方止痛药作为一种解脱的手段，但通常会上瘾并诉诸于更多潜在和危险的阿片类药物随着它们的容忍度的增加。放射性果实是一种新型的正电子发射断层扫描（PET）成像，我们正在作为生物标志物发展，以解决疼痛护理和治疗开发中的问题。我们最近在啮齿动物疼痛的啮齿动物模型中发表的发现证明了可以定位疼痛发生器的能力快速，准确，客观地测量其信号强度。我们的最终目标是：1）改变评估（实验）疼痛疗法，以及2）通过分子评估疼痛评估的护理标准成像。使用疼痛成像生物标志物技术将允许客观效率数据在临床试验中），并通过使较小的样本量降低成本，这是由于更均匀的种群，即具有特定的“疼痛信号”，并更准确地测量了镇痛作用。拟议的研究将在早期临床试验中评估放射性果实。成功的结果将为应用临床试验奠定阶段这进一步将这种诺言方法发展为一种有用的生物标志物来改变疼痛护理。