Daily & Localized NSAID Sonophoresis for Symptomatic Treatment of Knee Osteoarthritis

日常的

基本信息

批准号：
10413228
负责人：
George Kenneth Lewis
金额：
$ 143.86万
依托单位：
ZETROZ SYSTEMS, LLC
依托单位国家：
美国
项目类别：
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/10413228
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 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 Placebo Control 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 radiological imaging side effect standard of care study population symptom treatment treatment group ultrasound usability

项目摘要

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.

项目摘要：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，根据疾病控制中心和预防和国立卫生研究院。超过40％以上的人有症状的OA，并且由于疾病而降低了流动性。诸如保守的治疗方法（例如水治疗，步行，骑自行车和药物。定期使用NSAID可能会对心血管，胃肠道和肾脏系统。因此，局部NSAID经常被使用并提供类似的口服NSAIDS疼痛。长期超声已用于减轻疼痛并改善关节功能膝盖OA的患者。当超声与局部药物结合使用时，超声波该分子更深地进入组织，与单独的超声或局部相比，可改善疼痛的缓解单独使用NSAID。在SBIR I期中，我们开发了长期的低强度超声NSAID- 增强（1％双氯芬酸）的超声层贴片可用于老化的OA种群。我们首先证明了超声贴剂可以将包括水杨酸在内的NSAID的组织穿透增加3.5倍，并且与护理标准相比，双氯芬酸在3.8倍（p <0.01）。其次，在一项20受试者的人因素研究，以及一项针对射线照相患者的32个受试者OA临床研究轻度至中度的膝盖OA。在每日使用的7天中，有症状的疼痛大大减轻了 2.96点（70％）NRS（n = 24，p <0.001），所有受试者的NRS（50％）NRS（50％）NRS（n = 32，p = 0.02）。超过95％的研究人群发现该设备易于使用，并将继续治疗其膝盖OA 症状。对于此阶段II更新应用程序（1）第一个Zetroz系统将完善设计并优化老龄化人群的超声贴片用于保质期稳定性和设备功能/可用性。一系列调节测试标准包括敏化，细胞毒性，包装/配方稳定性，生物相容性，微生物的生长，保质期和家庭用途将在超声贴片上完成。另外，猪具有组织病理学的动物模型将完成，以验证设备的安全性。（2）Zetroz系统将完成为期8周的3臂，多站点，安慰剂对照，随机，功效研究，以扩展我们第一阶段研究通过检查300名患者的超声波斑的健康益处和商业性在三个种族不同的地方注册。研究的主要结果将是疼痛评分，评估每天使用数值评级量表（NRS）。基线NRS分数将包括研究的前两周没有干预。干预阶段将分开三个在人口统计学上等效的100组，分配使用活动/安慰剂的超声图片或标准双氯芬酸局外乳膏每日自我申请六个星期。拟议的组合疗法有可能提供安全，有效，并且 OA的保守治疗方法在老龄化人群中。