Targeted Temperature Modulation with Smart Radiometric Monitoring for Effective and Long-Lasting Opioid-Free Pelvic Pain Relief - A Novel Low-Cost, Portable, Tampon-sized Thermal Transfer Device.

通过智能辐射监测进行有针对性的温度调节，可有效且持久地缓解无阿片类药物的盆腔疼痛 - 一种新型低成本、便携式、卫生棉条大小的热转印设备。

• 批准号: 10760002
• 负责人: Zachary W Lyon
• 金额: $ 38.47万
• 依托单位: H3PELVIC THERAPY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760002
• 关键词: Absence of pain sensation; Acute; Acute Pain; Affect; Afferent Neurons; Analgesics; Anesthesia procedures; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Area; Atopobium vaginae; Bladder; Chronic Prostatitis; Clinical; Computer software; Data; Devices; Economics; Effectiveness; Energy Transfer; Eucalyptol; Excision; Family; Family member; Family suidae; Feedback; Food; Frequencies; Goals; Happiness; Heating; Histology; Hospitals; Human; Increased frequency of micturition; Interstitial Cystitis; Life; Link; Machine Learning; Membrane; Menthol; Monitor; Mucous Membrane; Muscle Cramp; Muscle strain; Needles; Nociceptors; Normalcy; Opioid; Outcome; Overactive Bladder; Pain; Pain management; Pathway interactions; Patients; Pelvic Pain; Pelvic floor structure; Pelvis; Performance; Peripheral; Personal Satisfaction; Pharmaceutical Preparations; Phase; Productivity; Psychotropic Drugs; Public Health; Quality of life; Radiometry; Rectum; Refractory; Resources; Schools; Sensory Receptors; Sex Behavior; Spasm; Suicide; System; TRP channel; Tampons; Technology; Temperature; Testing; Therapeutic; Thermal Conductivity; Thermometry; Time; Tissues; Topical application; Urinary tract infection; Urination; Vagina; Validation; Visceral; Water; Woman; Work; chronic pain; chronic pelvic pain; clinical translation; cohort; cost; design; disabling symptom; drinking water; effective therapy; endometriosis; functional electrical stimulation; improved; men; microwave electromagnetic radiation; micturition urgency; neural stimulation; novel; opioid abuse; optimal treatments; overdose death; pain reduction; pain relief; patient home care; patient oriented; portability; pre-clinical; prototype; receptor; rectal; sensor; skin burn; socioeconomics; somatosensory; success; targeted delivery; treatment planning

ABSTRACT Pelvic pain (PP) is associated with more than 20 different, clinically identified, maladies, such as Urinary Tract Infection (UTI), Menstrual Cramps (MC), Endometriosis (EM), Overactive Bladder (OAB) and Interstitial cystitis/Painful bladder syndrome (IC/PBS). These painful and debilitating conditions often have a dramatic negative impact on the quality of life (QOL) of millions of PP sufferers, from decreased work productivity and school performance, to declined sexual life and happiness. PP has been also associated with increased abuse of opioids and psycho-pharmaceuticals, ultimately leading to death by overdose and suicides. In addition to the burden to patients and their family, the economic direct and indirect PP cost is a significant fraction (>20%) of the 635B$ linked to chronic pain in US. Globally, pelvic pain affects one in five women and one in twelve men. Although treatments, including neural stimulation, are available, they are costly and lose effectiveness over time in >30% of patients. Patients with current untreatable chronic PP require a novel treatment approach that can relieve them from their debilitating symptoms. Significant relief of pain and reduced urination frequency has been recently associated with thermal modulation of pelvic floor. H3Pelvic has successfully developed a Contrast Applied Therapy (CAT) system modulating rapidly and comfortably temperature (cold/warm) via a water- circulating perineal membrane in a soft seat. When a properly sized vaginal or rectal probe with superior thermal conductivity is combined with the CAT system, the pain relief can be remarkable: an initial cohort of patients with refractory IC, unresponsive to drugs or neural stimulation, with a daily 45min vaginal cooling, resumed normal undertakings, restarted school, work and sexual activity, leading to an overall happier and productive life. We propose to optimize a probe design to maximize targeted delivery of thermal modulation using heatpipe technology, including real-time temperature tracking by passive microwave radiometry. RICAT (Radiometry Integrated CAT) will use probe-integrated smart radiometry to monitor deep tissue temperature. By leveraging machine learning, a minimal set of sensors shall accurately reconstruct temperature in the target region and maximize pain reduction. The Specific Aims for this first Phase are: 1) Optimally integrate radiometric sensors and smart planning/control software in a RICAT prototype; 2) Compare radiometric profiles with invasive needle sensors and perform histology in ex-vivo tissues and 7 pigs undergoing vaginal or rectal cooling/warming cycle. The goal of this Phase I is to integrate radiometric sensing into the thermal probe and test the probe’s ability to deliver consistent cooling and heating in the pelvic region in pre-clinical settings using healthy pigs. The data collected will allow us to move to Phase II, which will include a human trial in refractory IC patients. We expect that the animal study will show that RICAT optimally delivers pain-relieving thermal modulation to the pelvic region(s) effectively and reliably. Successful Phase I completion will pave the path towards clinical translational of a safe and effective pain-relieving technology to millions of patients suffering from debilitating pelvic pain.

抽象的 骨盆疼痛（PP）与20多种不同的，临床上的疾病（例如尿路）有关 感染（UTI），月经痉挛（MC），子宫内膜异位症（EM），过度活跃（OAB）和间隙 膀胱炎/疼痛膀胱综合征（IC/PBS）。这些痛苦和令人衰弱的条件通常具有戏剧性 对数百万PP患者的生活质量（QOL）的负面影响，从工作效率提高和 学校表现，拒绝性生活和幸福。 PP也与滥用增加有关 阿片类药物和心理药物，最终导致过量和自杀死亡。除了 伯恩对患者及其家人，经济直接和间接的PP成本是很大一部分（> 20％） 635b $与我们的慢性疼痛有关。在全球范围内，骨盆疼痛会影响五分之一的女性和十二分之一的男性。 尽管可以提供包括神经刺激在内的治疗，但它们的成本很高，并且随着时间的流逝而失去效力 在> 30％的患者中。当前患有无法治疗的慢性PP的患者需要一种新的治疗方法 减轻他们的衰弱症状。明显缓解疼痛和排尿频率的降低是 最近与骨盆底的热调节有关。 H3pelvic成功地开发了对比度 应用疗法（CAT）系统通过水调节迅速舒适的温度（冷/温暖） 在柔软的座椅中循环会阴膜。当适当尺寸的阴道或直肠探针带有上热的探针 电导率与CAT系统结合在一起，缓解疼痛可能很显着：初始患者队列 难治性IC，对药物或神经刺激无反应，每天进行45分钟的阴道冷却，恢复正常 承诺，重新开始学校，工作和性活动，从而带来整体的幸福和生产力。 我们建议优化探针设计，以最大程度地利用热管的靶向递送热调制 技术，包括被动微波辐射测定法的实时温度跟踪。 RICAT（辐射测定法） 综合猫）将使用探针集成的智能辐射测定法来监测深层组织温度。通过利用 机器学习，最小的传感器集应准确地重建目标区域的温度 减轻疼痛。第一阶段的具体目的是：1）最佳集成的辐射传感器 以及RICAT原型中的智能计划/控制软件； 2）将辐射谱与侵入性针比较 传感器并在发生阴道或直肠冷却/变暖循环的7个猪和7头猪中进行组织学。 该阶段I的目的是将辐射量传感整合到热探针中，并测试探针的能力 使用健康的猪在临床前的环境中在骨盆区域提供一致的冷却和加热。数据 收集的将使我们能够进入II期，其中包括在难治性IC患者中进行人体试验。我们期望 该动物研究将表明，RICAT最佳地将疼痛的热调节提供给骨盆 区域有效，可靠。成功的第一阶段完成将为临床翻译铺平道路 数百万患有使人衰弱的骨盆疼痛的患者安全有效的疼痛技术。