Optimizing ablation of cervical precancer with ethyl cellulose ethanol to enable translation to women in low and middle-income countries

使用乙基纤维素乙醇优化宫颈癌前病变消融术，以惠及低收入和中等收入国家的女性

• 批准号: 10821975
• 负责人: Brian Crouch
• 金额: $ 90.96万
• 依托单位: CALLA HEALTH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-14 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10821975
• 关键词: Ablation; Acute; Address; Adverse event; Affect; Alcohol consumption; Biological Assay; Businesses; Cellulose; Cervical; Cervix Uteri; Cessation of life; Clinic; Clinical; Clinical Research; Cold Therapy; Communities; Complex; Country; Data; Deposition; Diagnosis; Diameter; Disease; Electrocoagulation; Ensure; Ethanol; Excision; Family suidae; Formulation; Foundations; Funding; Gel; Goals; Grant; Health; Hour; Human; Income; Injectable; Injections; Institution; Interview; Investigational New Drug Application; Length; Lesion; Link; Liquid substance; Liver neoplasms; Low income; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Modeling; Monitor; Necrosis; Needles; Nitrogen; Outcome; Pelvis; Phase; Polymers; Power Sources; Protocols documentation; Provider; Public Health; Quality Control; Radiofrequency Interstitial Ablation; Recurrence; Research; Research Design; Small Business Innovation Research Grant; Stains; Sterility; Surveys; Technology; Testing; Therapeutic; Time; Tissues; Toxic effect; Translations; Vial device; Vision; Woman; Work; X-Ray Computed Tomography; cervical cancer prevention; combinatorial; conventional therapy; cost; design; disability-adjusted life years; experimental study; improved; interest; intervention cost; loop electrosurgical excision procedure; low and middle-income countries; manufacture; medically underserved; mortality; point of care; population health; potency testing; premalignant; pressure; prevent; prototype; safety assessment; screening; stability testing; tool; treatment arm; underserved area; usability

Abstract Cervical cancer affects the lives of half a million women worldwide each year, and over half of these women die. Preventative solutions that are widely used in wealthy countries are not practical for use in medically underserved regions due to sophisticated technologies and expertise needed to sustain these solutions. Thus, alternative protocols that employ low-cost, simple-to-use technologies are needed to prevent cervical cancer. Our vision is to develop high quality, low-cost interventions that will be effective in low and middle-income countries (LMICs) to address shortcomings of current solutions for cervical cancer prevention. The Calla Health Foundation is developing the tools needed to help meet the WHO metrics for cervical cancer elimination in the next 100 years. Under fast track SBIR funding (R44CA240019), we are developing tools for point-of-care screening and diagnosis. However, screening and diagnosis alone will not lead to decreases in cervical cancer mortality if access to point-of-care treatment remains limited. While Loop Electrosurgical Excision procedure (LEEP) is the most widely used treatment in high-income settings, cryotherapy is more commonly used in LMICs. Recently, thermocoagulation has gained acceptance for ablation of cervical pre-cancer as it does not require consumables (continuous supply of pressurized liquid nitrogen for cryotherapy) or a stable power supply (for LEEP). However, thermocoagulation is limited by bioheat transfer and therefore the depth of necrosis it can achieve. To develop a complementary therapeutic approach to thermocoagulation, the goal of our Phase I SBIR grant was to establish an injectable low-cost ablative therapy based on controlled delivery of a ubiquitous agent, ethanol to treat cervical pre-cancer. Specifically, we developed a new formulation of ethanol using a polymer called ethyl cellulose (EC) to act as a slow-release gel limiting off target toxicity and an automated injector to reliably deliver ethanol into the region of interest. Moving forward, the goal of our Phase II SBIR grant is to develop beta versions of the automated injector, develop packaging and quality control metrics for EC-ethanol, and assess if a combinatorial therapy in which sequential EC-ethanol ablation and thermocoagulation are applied to the cervix is synergistic and enhances efficacy. This work will include the following specific aims: 1) evaluate usability and repeatability of hand-held injectors for EC-ethanol delivery; 2) establish EC-ethanol stability and potency testing plan and release criteria; 3) assess safety and efficacy of sequential EC-ethanol ablation and thermocoagulation compared to monotherapies; and 4) assess clinical workflow and population health impact of monotherapies and combinatorial therapy.

摘要 宫颈癌每年影响全球50万妇女的生活，其中超过一半的妇女死亡。 在富裕国家广泛使用的预防性解决方案对于医疗服务不足的人来说是不现实的 由于维持这些解决方案所需的尖端技术和专业知识，这些国家和地区的经济和社会发展受到了影响。因此，替代方案 采用低成本、易用技术的方案是预防宫颈癌所必需的。我们的愿景是 制定在低收入和中等收入国家有效的高质量、低成本的干预措施 以解决目前宫颈癌预防解决方案的不足。卡拉健康基金会是 开发必要的工具，以帮助满足世卫组织在未来100年内消除宫颈癌的指标。 在快速通道SBIR资金(R44CA240019)下，我们正在开发用于护理点筛查和 诊断。然而，在以下情况下，仅靠筛查和诊断并不能降低宫颈癌死亡率 获得护理点治疗的机会仍然有限。而环状电切术(LEEP)是 冷冻疗法在高收入人群中应用最为广泛，但在LMICs中使用更为普遍。最近， 热凝术由于不需要消耗品，已被接受用于宫颈癌前病变的消融 (连续供应用于冷冻治疗的加压液氮)或稳定的电源(用于LEEP)。然而， 热凝受到生物热传递的限制，因此它可以达到的坏死深度是有限的。发展，发展 作为热凝的一种补充治疗方法，我们第一阶段SBIR赠款的目标是建立 一种可注射的低成本消融疗法，基于无处不在的药物乙醇的控制释放，用于治疗宫颈 癌症前科。具体地说，我们开发了一种新的乙醇配方，使用一种名为乙基纤维素(EC)的聚合物 充当限制目标毒性的缓释凝胶和自动注射器，可靠地将乙醇输送到 感兴趣的区域。展望未来，我们第二阶段SBIR赠款的目标是开发 自动注射器，开发EC-乙醇的包装和质量控制指标，并评估组合 将EC-乙醇消融和热凝应用于宫颈的治疗是协同的。 提高药效。这项工作将包括以下具体目标：1)评估可用性和重复性 2)建立EC-乙醇稳定性和效力测试计划，并 释放标准；3)评估序贯EC-乙醇消融和热凝的安全性和有效性 与单一疗法相比；以及4)评估单一疗法的临床工作流程和人群健康影响 综合疗法。