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.

项目概要：骨关节炎 (OA) 是最常见的关节炎类型，影响美国超过 3000 万成年人根据疾病控制中心和疾病控制中心的数据，2015 年，占医疗机构就诊次数的 25% 以上预防和国立卫生研究院。超过 40% 的 65 岁以上个体患有 OA 症状由于疾病而导致活动能力下降。骨关节炎疼痛通常可通过保守治疗方法缓解，例如水疗法、步行、骑自行车和药物治疗。经常使用非甾体抗炎药会对身体产生不良副作用心血管、胃肠道和肾脏系统。因此，经常使用外用非甾体抗炎药，并提供类似的作用口服非甾体抗炎药可缓解疼痛。长时间超声波已被用于减轻疼痛并改善关节功能膝关节骨关节炎患者。当超声波与局部药物结合使用时，超声导入会驱动分子深入组织，与单独超声或局部超声相比，可改善疼痛缓解效果单独应用 NSAIDs。在我们的 SBIR 第一阶段，我们开发了一种长持续时间低强度超声 NSAID- 增强型（1% 双氯芬酸）超声导入贴片，供老年 OA 人群使用。我们首先证明了超声导入贴片可以将包括水杨酸在内的非甾体抗炎药的组织渗透性提高 3.5 倍与标准护理相比，双氯芬酸增加了 3.8 倍 (p<0.01)。其次，对超声导入贴片进行了评估一项 20 名受试者的人为因素研究，以及一项针对经放射学确诊的患者的 32 名 OA 临床研究轻度至中度膝关节骨关节炎。在每天使用 4 小时的短短 7 天内，症状性疼痛就显着减轻了响应者为 2.96 分 (70%) NRS (n=24，p<0.001)，所有受试者为 2.03 分 (50%) NRS (n=32，p=0.02)。超过 95% 的研究人群发现该设备易于使用，并将继续治疗膝关节骨关节炎症状。对于本次二期更新申请 (1)，First ZetrOZ Systems 将完善设计并优化超声导入贴片可提高老年人的保质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、微生物的生长、保质期和家庭使用都将在超声波导入贴片上完成。另外，还有一只猪将完成具有组织病理学的动物模型，以验证该设备的安全性。 (2) ZetrOZ系统将完成一项为期 8 周、三臂、多部位、安慰剂对照、随机、功效研究，以扩展我们的研究 I 期研究通过检查超声导入贴片对 300 名患者的健康益处和商业性在三个不同种族的地点注册。研究的主要结果将是评估疼痛评分每天使用数字评分量表 (NRS)。基线 NRS 分数将包括研究的前两周无需干预。干预阶段将分成三个人口统计相当的组（每组 100 人），被分配使用活性/安慰剂超声导入贴片或标准双氯芬酸外用乳膏，每日自我治疗申请了六周。所提出的联合疗法有可能提供安全、有效和老龄化人群中 OA 的保守治疗方法。