Portable, low-cost cryotherapy system that does not require consumable cryogen gas for the treatment of cervical precancerous lesions

便携式、低成本冷冻治疗系统，无需消耗冷冻剂气体即可治疗宫颈癌前病变

• 批准号: 10602226
• 负责人: Wei-Hsiang Chang
• 金额: $ 39.66万
• 依托单位: ANANYA HEALTH INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-12 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10602226
• 关键词: Ablation; Adopted; Adoption; Agar; Age; Area; Cancer Etiology; Caregivers; Cervical; Cervical Cancer Screening; Cessation of life; Clinic; Clinical; Cold Therapy; Country; Dependence; Development; Devices; Disease Progression; Electricity; Ensure; Environment; Equipment; Foundations; Freezing; Gases; Gel; Generations; Global Warming; Goals; Gold; Health; Health Status; Health care facility; Hospitals; Human Papillomavirus; Income; Infrastructure; Interview; Lesion; Liquid substance; Local anesthesia; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Manufacturer Name; Modeling; Pain; Patients; Performance; Persons; Phase; Physicians; Play; Primary Health Care; Procedures; Resource-limited setting; Resources; Risk; Role; Savings; Services; Sheep; Small Business Innovation Research Grant; System; Technology; Temperature; Testing; Thermal Ablation Therapy; Thick; Tissue Model; Tissues; Training; United States National Institutes of Health; Uterus; Vaccination; Vaccines; Visit; Woman; Work; World Health Organization; analog; base; clinical infrastructure; clinical research site; commercialization; cost; cost effective; cryogenics; design; design verification; effective therapy; evaporation; experience; fitness; health goals; innovation; interest; loop electrosurgical excision procedure; low and middle-income countries; low income country; mortality; necrotic tissue; phase change; portability; premalignant; prevent; prototype; remote location; success; treatment response; treatment services; tumor progression; unvaccinated; usability

Abstract While cervical cancer deaths have dramatically fallen in high-income countries, cervical cancer is one of the leading causes of cancer deaths in low- and middle-income countries (LMICs). Cervical cancer accounted for 341,800 deaths in 2020, with approximately 90% of these deaths occurring in LMICs. Treatments for precancerous lesions are highly effective for preventing cancer progression, so the key is to identify and treat lesions early. However, most low-income countries that offer cervical cancer screening lack accessible treatment services. The lack of readily accessible treatment options means referral of patients to larger hospitals, which is an obstacle to proper treatment, leading to disease progression to cancer. While loop electrosurgical excision procedure is the gold standard in the treatment of lesions, it requires highly trained clinicians and an operating environment rarely found in LMIC clinics. The World Health Organization recommends cryotherapy for cervical precancer treatment in LMICs, but the key drawback for current cryotherapy systems is their dependence on consumable cryogen gas. Access to a cryogen gas supply is unreliable, consumable gas costs are high, and heavy and bulky gas cylinders limit portability to remote clinics. Other LMIC-targeted options have been attempted, but they were poorly adopted due to high cost and discontinued manufacturer support (CryoPen) or insufficient depth of tissue necrosis for fully effective treatment (heat-based thermal ablation). Taken together, no single system exists to provide an appropriate and cost-effective solution that is suitable for widespread LMIC use. With an LMIC-appropriate treatment solution, cervical cancer mortality could be reduced by 33% (~300,000 deaths) by 2030. With NIH SBIR Phase I support, Ananya Health’s goal is developing the Ala System, a portable, battery-powered, closed-loop cryotherapy system for the treatment of cervical precancerous lesions in LMICs. By recirculating the cryogen fluid in a closed-loop system, the Ala System eliminates the need for consumable cryogen gas. The rechargeable battery allows for treatment independent of electrical grid availability. Preliminary studies have shown we can achieve tissue-freezing temperatures on an ovine uterus tissue model with a battery- powered closed-loop prototype. For this proposal, first, we will use a benchtop cervical model to further optimize system parameters to meet the established cervical tissue cryotherapy requirement: ≥5 mm depth of tissue reaches ≤-20°C for ≥1 min in a ≤5 min procedure (Specific Aim 1). Second, we will make in-person visits to two LMIC clinical sites to interview and observe ≥6 clinicians to identify critical User Needs and system requirements to ensure the Ala System design will suit the clinical, usability, and operational needs of primary care facilities in LMICs (Specific Aim 2). The development work in Phase I will lay the foundation for final device testing, user design validation, and regulatory approvals via FDA 510(k) in Phase II, followed by widespread deployment of the Ala System through global NGOs and local and regional LMIC organizational partnerships.

抽象的 虽然高收入国家的宫颈癌死亡率大幅下降，但宫颈癌是导致宫颈癌死亡的主要原因之一。 宫颈癌是低收入和中等收入国家癌症死亡的主要原因。 2020 年将有 341,800 人死亡，其中约 90% 发生在中低收入国家。 癌前病变对于预防癌症进展非常有效，因此关键是识别和治疗 然而，大多数提供宫颈癌筛查的低收入国家缺乏可用的治疗方法。 缺乏便捷的治疗选择意味着将患者转诊至较大的医院。 适当治疗的障碍，导致疾病进展为癌症。 程序是治疗病变的黄金标准，它需要训练有素的步兵和操作人员 世界卫生组织建议对宫颈癌进行冷冻治疗。 中低收入国家的前体治疗，但当前冷冻治疗系统的主要缺点是它们依赖于 消耗性制冷剂气体的供应不可靠，消耗性气体成本高，并且 笨重的气瓶限制了偏远诊所的便携性。 尝试过，但由于成本高和制造商停止支持（CryoPen）而未能得到很好的采用，或者 组织坏死深度不足以进行充分有效的治疗（基于热的热消融）。 不存在单一系统可以提供适合广泛的中低收入国家的适当且具有成本效益的解决方案 使用适合 LMIC 的治疗解决方案，宫颈癌死亡率可降低 33%（约 300,000）。 到 2030 年，在 NIH SBIR 第一阶段的支持下，Ananya Health 的目标是开发 Ala 系统，这是一种便携式、 电池供电的闭环冷冻治疗系统，用于治疗中低收入国家的宫颈癌前病变。 通过在闭环系统中再循环冷冻剂流体，Ala 系统无需消耗品 可充电电池允许独立于电网的初步可用性进行治疗。 研究表明，我们可以使用电池在绵羊子宫组织模型上实现组织冷冻温度 对于这个提案，我们首先将使用台式颈椎模型来进一步优化。 满足既定宫颈组织冷冻治疗要求的系统参数：组织深度≥5毫米 在 ≤5 分钟的程序中达到 ≤-20°C ≥1 分钟（具体目标 1）。 LMIC 临床站点采访和观察 ≥6 名指挥官，以确定关键的用户需求和系统要求 确保 Ala 系统设计能够满足初级保健机构的临床、可用性和操作需求 LMIC（具体目标 2）。第一阶段的开发工作将为用户的最终设备测试奠定基础。 第二阶段的设计验证和 FDA 510(k) 的监管批准，随后广泛部署 通过全球非政府组织以及地方和区域中低收入国家组织伙伴关系建立阿拉系统。