Daily & Localized NSAID Sonophoresis for Symptomatic Treatment of Knee Osteoarthritis

日常的

• 批准号: 10264115
• 负责人: George Kenneth Lewis
• 金额: $ 142.79万
• 依托单位: ZETROZ SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264115
• 关键词: Adoption; Adult; Adverse effects; Affect; Age-Years; Aging; Americas; Animal Model; Arthritis; Articular Range of Motion; Businesses; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Client satisfaction; Clinical; Clinical Research; Clinical Trials; Clinical effectiveness; Combined Modality Therapy; Complex; Cost Effectiveness Analysis; Coupled; Coupling; Cream; Data; Degenerative polyarthritis; Devices; Diagnostic radiologic examination; Diclofenac; Disease; Double-Blind Method; Drug Delivery Systems; Drug Utilization; Effectiveness; Engineering; Enrollment; Exercise; Family suidae; Formulation; Growth; Health Benefit; Health Professional; Histopathology; Home; Hour; Human body; Individual; Insurance Carriers; Insurance Coverage; Intervention; Joints; Kidney; Knee Osteoarthritis; Laboratories; Life; Location; Measures; Medical; Multi-Institutional Clinical Trial; Non-Steroidal Anti-Inflammatory Agents; Numeric Rating Scale; Office Visits; Oral; Outcome Measure; Outcome Study; Pain; Pain management; Participant; Patients; Penetration; Pharmacologic Substance; Phase; Placebos; Population; Production; Quality of life; Randomized; Regulatory Pathway; Safety; Salicylic Acids; Series; Site; Small Business Innovation Research Grant; Statistical Data Interpretation; Symptoms; System; Technology; Testing; Therapeutic; Tissues; Topical application; Transdermal substance administration; Ultrasonic Therapy; Ultrasonography; United States; United States National Institutes of Health; Validation; Walking; Water; Western Ontario and McMaster Universities Arthritis Index; active method; aging population; arm; base; biomaterial compatibility; celecoxib; commercialization; comorbidity; cytotoxicity; design; disability; efficacy study; ethnic diversity; experience; functional improvement; gastrointestinal; human subject; improved; indexing; innovation; joint function; manufacturability; microbial; minimal risk; osteoarthritis pain; overtreatment; pain reduction; pain relief; pain scale; pain score; phase 1 study; placebo controlled study; placebo group; primary outcome; side effect; standard of care; study population; symptom treatment; treatment group; usability

Project Summary: Osteoarthritis (OA) is the most common type of arthritis, affecting over 30 million adults in the United States in 2015 and represents over 25% of medical office visits according to the Centers for Disease Control and Prevention and the National Institutes of Health. Over 40% of individuals over 65 have symptomatic OA and reduced mobility due to the disease. OA pain is often mitigated with conservative treatment approaches such as water therapy, walking, cycling, and pharmaceuticals. Regular use of NSAIDs can have adverse side effects on cardiovascular, gastrointestinal and renal systems. As such, topical NSAIDs are often used and provide similar pain relief to oral NSAIDs. Long-duration ultrasound has been used to reduce pain and improve joint function in patients with knee OA. When ultrasound is used in conjunction with topical pharmaceuticals, sonophoresis drives the molecules deeper into tissue, providing improved pain relief compared to ultrasound alone or topical application of NSAIDs alone. In our SBIR Phase I, we developed a long-duration low-intensity ultrasound NSAID- enhanced (1% diclofenac) sonophoresis patch for use by the aging OA population. We first demonstrated that the sonophoresis patch could increase tissue penetration of NSAIDs including salicylic acid by 3.5x and diclofenac by 3.8x compared to standard of care (p<0.01). Secondly, the sonophoresis patch was evaluated in a 20-subject human-factors study, and a 32-subject OA clinical study on patients with radiographically confirmed mild to moderate knee OA. In only 7-days of daily 4-hour use, symptomatic pain was significantly reduced by 2.96 point (70%) NRS (n=24, p<0.001) for responders and 2.03 point (50%) NRS (n=32, p=0.02) for all subjects. Over 95% of the study population found the device easy to use and would continue treatment for their knee OA symptoms. For this Phase II renewal application (1) First ZetrOZ Systems will refine the design and optimize the sonophoresis patch for shelf-life stability and device functionality/usability by the aging population. A series of regulatory testing standards including sensitization, cytotoxicity, packaging/formulation stability, biocompatibility, microbial growth, shelf-life and home-use will be completed on the sonophoresis patch. Additionally, a porcine animal model with histopathology will be completed to verify the safety profile of the device. (2) ZetrOZ Systems will complete an 8-week, 3-arm, multi-site, placebo-controlled, randomized, efficacy study to expand upon our Phase I study by examining the health benefits and commerciality of the sonophoresis patch in 300 patients enrolled at three ethnically diverse locations. The primary outcome of the study will be pain score, evaluated daily using the numerical rating scale (NRS). Baseline NRS score will include the first two weeks of the study without intervention. The intervention phase will separate three demographically equivalent groups of 100, assigned to use either the active/placebo sonophoresis patch or standard diclofenac topical cream daily self- applied for six weeks. The proposed combination therapy has the potential to deliver a safe, effective, and conservative treatment approach for OA in the aging population.

项目概要： 骨关节炎（OA）是最常见的关节炎类型，在美国影响超过3000万成年人， 2015年，根据疾病控制中心的数据， 预防和国立卫生研究院。超过40%的65岁以上的人患有症状性OA， 由于疾病导致的活动减少。OA疼痛通常通过保守治疗方法缓解，例如 水疗、散步、骑自行车和药物。定期使用NSAIDs可能会产生不良副作用， 心血管、胃肠道和肾脏系统。因此，经常使用局部NSAID，并提供类似的 口服NSAID缓解疼痛。长时间超声已被用于减轻疼痛和改善关节功能， 膝关节OA患者。当超声波与局部药物结合使用时， 分子深入组织，与单独或局部超声相比， 单独使用NSAIDs。在我们的SBIR I期，我们开发了一种长时间低强度超声NSAID- 增强型（1%双氯芬酸）超声促渗贴剂，用于老年OA人群。我们首先证明， 超声促渗贴片可以使包括水杨酸在内NSAID的组织渗透增加3.5倍， 与标准治疗相比，双氯芬酸增加了3.8倍（p<0.01）。第二，超声促渗贴片被评估为 一项20例受试者人为因素研究和一项32例受试者OA临床研究，研究对象为经影像学证实的 轻度至中度膝关节OA。在仅仅7天的每天4小时的使用中，症状性疼痛显著减轻， 2.96反应者的NRS为2.03分（70%）（n=24，p<0.001），所有受试者的NRS为2.03分（50%）（n=32，p=0.02）。 超过95%的研究人群认为该器械易于使用，并将继续治疗其膝关节OA 症状对于第二阶段的更新申请，（1）First ZetrOZ Systems将完善设计并优化 超声促渗贴片用于老化人群的货架期稳定性和设备功能/可用性。一系列 监管测试标准，包括致敏性、细胞毒性、包装/制剂稳定性、生物相容性， 微生物生长、保质期和家庭使用将在超声促渗贴片上完成。此外，一头猪 将完成具有组织病理学的动物模型，以验证器械的安全性。(2)ZetrOZ系统 将完成一项为期8周、3组、多中心、安慰剂对照、随机、疗效研究，以扩展我们的 通过检查300名患者的超声促渗贴片的健康益处和商业性进行的I期研究 在三个不同种族的地方注册。研究的主要结局将是疼痛评分， 每天使用数字评分量表（NRS）。基线NRS评分将包括研究的前两周 没有干预。干预阶段将分为三个人口统计学上相当的组，每组100人， 分配每日自我使用活性/安慰剂超声促渗贴剂或标准双氯芬酸外用乳膏， 申请了六个星期。所提出的组合疗法具有提供安全、有效且 老年人群中OA的保守治疗方法。