Image-Guided Transurethral HIFU for Genitourinary Therapy

图像引导经尿道 HIFU 泌尿生殖治疗

• 批准号: 10452639
• 负责人: Everette C Burdette
• 金额: $ 46.88万
• 依托单位: ACOUSTIC MEDSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452639
• 关键词: Abdomen; Acoustics; Acute; Address; Adult; Affect; American; Anatomy; Anesthetics; Animals; Businesses; Cadaver; Catheters; Childbirth; Clinical; Clinical Research; Coagulation Process; Collagen; Computer software; Connective Tissue; Consultations; Data; Development; Development Plans; Device Designs; Devices; Disease; Dose; Ensure; Evaluation; Exercise; Exertion; Expenditure; Extravasation; Fascia; Female urethral structure; Focused Ultrasound; Freedom; Freezing; Future; Genitourinary system; Goals; Heating; Histologic; Histology; Human; Implant; Intellectual Property; Legal patent; Licensing; Lifting; Ligaments; Marketing; Medical; Mental Depression; Mental Health; Methods; Modeling; Modification; Morbidity - disease rate; Mucous Membrane; Natural regeneration; Operative Surgical Procedures; Outpatients; Palliative Care; Patients; Pattern; Pelvic floor structure; Pelvis; Penetration; Performance; Pharmacologic Substance; Phase; Preparation; Procedures; Radial; Readiness; Recovery; Safety; Scanning; Side; Sterility; Sterilization; Stress Urinary Incontinence; Structure; Study models; Surgical incisions; Symptoms; System; Techniques; Technology; Temperature; Testing; Therapeutic; Therapeutic Intervention; Thermal Ablation Therapy; Time; Tissues; Tubular formation; Ultrasonic Therapy; Ultrasonography; Urethra; Urinary Incontinence; Urine; Vagina; Validation; Woman; Women' s Health; Work; alternative treatment; base; clinical implementation; clinical investigation; commercialization; cost; cost effectiveness; curative treatments; design; dosimetry; ewe model; experimental study; healing; human female; human model; human subject; image guided; in silico; in vivo; innovation; interstitial; manufacturing process; minimally invasive; new technology; palliative; payment; personalized medicine; phantom model; phase 2 study; preclinical study; pressure; process optimization; protocol development; reduce symptoms; response; safety study; self esteem; side effect; simulation; soft tissue; treatment optimization; treatment planning; treatment strategy; ultrasound; urinary; vaginal mucosa

Abstract Stress urinary incontinence (SUI) in women is an increase of pelvic floor compliance which results in decreased urethral pressure, typically through childbirth, and presents as urine leakage during abdominal strain. SUI has significant impact on women’s health, including an association with increased levels of depression. Curative options are limited to the invasive surgical insertion of a tape implant which limits the mobility of the urethra. Bulking agents injected in the peri-urethral tissue are a longstanding effective but temporary treatment. Pharmaceuticals are relatively new, prohibitively expensive, and there is no track record of long-term efficacy and negative side effects can occur. Approximately 14 million women are relegated to the palliative approaches of wearing absorptive pads or diapers through the day. A substantial clinical need exists for a noninvasive alternative to traditional surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Recent clinical investigations of minimally-invasive thermal techniques have demonstrated targeted thermal modification and stiffening of pelvic tissue can reduce symptoms of SUI. These techniques have shown promise, but are more invasive than the current surgical options and are less effective. Our Phase II development study showed encouraging in vivo results suggesting that our innovative therapeutic ultrasound catheter based noninvasive technology can efficiently deliver thermal therapy at the target tissue of endopelvic fascia without damaging surrounding tissue (vaginal and urethal wall), based on histopathological analysis, with demonstrated capabilities to provide dynamic spatial control of selective heating patterns, well-controlled radial thermal penetration, and fast treatment times. In comparison to existing thermal approaches, our Phase II results clearly demonstrate a significant advance in technology and approach for treating SUI with the promise of more accurate and thorough targeting of heat-induced collagen regeneration, protection of critical non-targeted tissue (e.g., urethral and vaginalmucosa), short procedure times, and thereby increasing accessibility to a larger number of SUI patients. The objective of this Phase IIB plan is to design-freeze our therapy applicator design and then conduct a GLP in-vivo study with our ultrasound SUI catheter and FDA 510(k) cleared TheraVision® system for data to support a follow-on clinical study under FDA Guidance and to further build additional strong intellectual property around the technology. Market analyses will be conducted to develop strategies leading to commercialization. Device design, bench experiments, biothermal and acoustic modeling, together with experimental testing in both human female pelvis cadaveric studies and an in-vivo GLP compliant study in ewes GU tract, combined with workflow study will be conducted to freeze device design, extensively characterize device performance, and applied to potential treatment approaches in preparation for the ultimate goal of product finalization and clinical implementation. Devices will be manufactured under our existing ISO compliant Quality Management System.

抽象的 女性压力性尿失禁 (SUI) 是盆底顺应性增加，导致 尿道压力降低，通常是在分娩过程中，并表现为腹部尿液渗漏 拉紧。 SUI 对女性健康有重大影响，包括与 沮丧。治疗选择仅限于侵入性手术插入胶带植入物，这限制了 尿道的活动度。注射到尿道周围组织的填充剂是一种长期有效但 临时治疗。药品相对较新，价格昂贵，而且没有跟踪记录 长期疗效和负面副作用可能会发生。大约有 1400 万女性被降级到 全天佩戴吸收垫或尿布的姑息疗法。存在大量临床需求 寻找传统手术方法的无创替代方案，有望降低发病率并促进康复 时间、更快的手术时间和更低的成本。微创热疗的最新临床研究 技术已证明有针对性的热修改和骨盆组织硬化可以减少 SUI 的症状。这些技术已显示出希望，但比目前的手术更具侵入性 选项且效果较差。我们的 II 期开发研究显示出令人鼓舞的体内结果表明 我们基于创新的治疗性超声导管的无创技术可以有效地传递热量 针对骨盆内筋膜的目标组织进行治疗，而不损伤周围组织（阴道和尿道） wall），基于组织病理学分析，具有提供动态空间控制的能力 选择性加热模式、良好控制的径向热渗透以及快速的处理时间。相比之下 与现有的热方法相比，我们的第二阶段结果清楚地表明了技术的重大进步 以及治疗 SUI 的方法，有望更准确、更彻底地针对热诱发的症状 胶原蛋白再生，保护关键的非目标组织（例如尿道和阴道粘膜），短期 手术时间，从而增加更多 SUI 患者的可及性。此举的目的 IIB 期计划是设计冻结我们的治疗涂抹器设计，然后与我们进行 GLP 体内研究 超声 SUI 导管和 FDA 510(k) 批准 TheraVision® 系统的数据支持后续临床 在 FDA 指导下进行研究，并进一步围绕该技术建立更多强大的知识产权。 将进行市场分析以制定商业化战略。装置设计、工作台 实验、生物热和声学模型，以及对人类女性的实验测试 骨盆尸体研究和母羊 GU 道体内 GLP 合规研究，结合工作流程研究 将进行冻结器件设计，广泛表征器件性能，并应用于 为产品最终确定和临床的最终目标做准备的潜在治疗方法 执行。设备将根据我们现有的符合 ISO 标准的质量管理体系进行制造。