Enhanced ultrasound treatment of chronic wounds with monitoring of healing and quality of life outcomes

强化超声治疗慢性伤口，监测愈合情况和生活质量结果

• 批准号: 9473400
• 负责人: Peter A. Lewin
• 金额: $ 2.6万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-27 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9473400
• 关键词: Adjuvant Therapy; Affect; Artificial skin; Becaplermin; Biomedical Engineering; Blood Vessels; Blood flow; Caregivers; Caring; Characteristics; Chronic; Clinical; Custom; Data; Decubitus ulcer; Development; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic ulcer; Diagnostic; Diffuse; Discipline of Nursing; Disease; Double-Blind Method; Epidemiology; Exposure to; Foundations; Frequencies; Future; Generic Drugs; Guidelines; Health; Human; Impaired wound healing; Individual; Inflammation; Inflammatory; Interdisciplinary Study; Intervention; Link; Malnutrition; Measures; Methods; Mission; Monitor; Morbidity - disease rate; Near-Infrared Spectroscopy; Necrosis; Nurses; Nutritional; Nutritional status; Operative Surgical Procedures; Optical Methods; Optics; Outcome; Patients; Perfusion; Physics; Physiological; Placebos; Platelet-Derived Growth Factor; Quality of life; Randomized Clinical Trials; Randomized Controlled Trials; Research; Safety; Societies; Specificity; Surface; System; Testing; Therapeutic; Therapeutic Agents; Therapeutic Uses; Time; Tissues; Translating; Treatment Protocols; Ultrasonic Therapy; Ultrasonics; Ultrasonography; Varicose Ulcer; Work; Wound Healing; angiogenesis; blood perfusion; chronic wound; cost; cost effective; disability; effective therapy; evidence base; healing; health related quality of life; hemodynamics; improved; individualized medicine; innovation; light weight; non-healing wounds; noninvasive diagnosis; novel; novel therapeutics; nutrition; personalized medicine; portability; prevent; programs; reduce symptoms; standard care; tissue oxygenation; wound; wound closure

Project Summary / Abstract The two most common types of chronic wounds are venous ulcers (VUs) and diabetic ulcers (DUs). We will conduct the first double-blind randomized controlled trial (RCT) to test the effect of low-frequency, low- intensity (LFLI) ultrasound (US) on chronic wound healing and health related quality of life (HRQOL) with high statistical confidence (α < 0.05, power > 0.90, n=60 VUs, n=60 DUs). Our approach combines this active therapy with non-invasive diagnostic monitoring of wound hemodynamics throughout the treatment cycle, and includes analysis of the impact of nutritional status and inflammation on wound closure. There are several innovative aspects of this work. Specifically, (1) Our lightweight, battery-powered applicator is the first potentially wearable ultrasound wound therapy device that is safe to apply for extended periods of time. (2) The applicator actively promotes healing, which is fundamentally different from commercial ultrasonic systems that remove necrotic tissue only. (3) Our approach will link LFLI US exposure to changes in wound hemodynamics and HRQOL, which has the potential to enable personalized medicine. (4) Our analysis of patient nutritional and systemic inflammatory status may enable further treatment customization by identifying those patients most likely to benefit from LFLI US therapy. (5) Our approach incorporates both disease-specific and generic measures of HRQOL, which is unique for a therapeutic ultrasound RCT. Our low-frequency, low-intensity (20 kHz, <100 mW/cm2 spatial peak-temporal peak), portable ultrasound applicator is safe and clinically pragmatic wound treatment. The field lightweight (<25g) and permits parameters of our US device were previously optimized for venous ulcers, and our three recent pilot clinical human studies (VUs: n=20, n=25; DUs: n=10) demonstrated that our treatment improved healing by 15% per week compared to sham treatment. We therefore anticipate that our treatment will accelerate closure of chronic wounds, and we hypothesize that (1) LFLI US will improve generic and disease-specific HRQOL scores, (2) LFLI US will activate beneficial changes in the microvasculature of the wound and surrounding tissue, and (3) individuals with poor nutrition and high levels of inflammation will have delayed wound healing. Our specific aims are to: (1) Assess the effect of LFLI US on VUs and DUs by measuring wound closure as a primary endpoint and generic and disease-specific HRQOL as secondary endpoints. (2) Monitor the effects of LFLI US on wound perfusion and oxygenation using non-invasive optical methods, and (3) Determine the impact of nutritional status and inflammation on closure of DUs and VUs. Overall, this work will validate LFLI US as a safe, portable, and cost-effective therapy for chronic wounds. This is important because new therapies and improved clinical paradigms for wound management are urgently needed. Over the long-term, our findings may enable the development of personalized wound treatment regimens across care settings.

项目概要/摘要 两种最常见的慢性伤口类型是静脉性溃疡（VU）和糖尿病性溃疡（DU）。我们 将进行第一个双盲随机对照试验（RCT），以测试低频、低频率的效果 强度（LFLI）超声（美国）对慢性伤口愈合和健康相关生活质量（HRQOL）的影响 统计置信度（α < 0.05，功效 > 0.90，n=60 VU，n=60 DU）。我们的方法结合了这种主动 在整个治疗周期中对伤口血流动力学进行非侵入性诊断监测，以及 包括分析营养状况和炎症对伤口闭合的影响。有几个 这项工作的创新方面。具体来说，(1) 我们的轻型电池供电涂抹器是第一个 潜在的可穿戴超声伤口治疗设备，可以安全地长时间使用。 (2) 施用器积极促进愈合，这与商用超声波系统有根本不同 仅去除坏死组织。 (3) 我们的方法将 LFLI US 暴露与伤口变化联系起来 血流动力学和 HRQOL，有可能实现个性化医疗。 (4) 我们的分析 患者的营养和全身炎症状态可以通过识别来实现进一步的治疗定制 这些患者最有可能从 LFLI US 治疗中受益。 (5) 我们的方法结合了疾病特异性 HRQOL 的通用测量，这对于治疗性超声 RCT 来说是独一无二的。 我们的低频、低强度（20 kHz，<100 mW/cm2 空间峰值-时间峰值）便携式超声 施药器是一种安全且临床实用的伤口治疗方法。领域 重量轻（<25g）并且允许 我们美国设备的参数之前针对静脉溃疡进行了优化，我们最近的三个试点临床 人体研究（VU：n = 20，n = 25；DU：n = 10）表明，我们的治疗每增加15％的愈合 与假治疗相比一周。因此，我们预计我们的治疗将加速关闭 慢性伤口，我们假设 (1) LFLI US 将改善一般和特定疾病的 HRQOL 分数，(2) LFLI US 将激活伤口和周围微血管的有益变化 (3)营养不良和炎症水平高的人会延迟伤口愈合。 我们的具体目标是： (1) 通过测量伤口闭合来评估 LFLI US 对 VU 和 DU 的影响 作为主要终点，通用和特定疾病的 HRQOL 作为次要终点。 (2) 监控 使用非侵入性光学方法确定 LFLI US 对伤口灌注和氧合的影响，以及 (3) 确定 营养状况和炎症对 DU 和 VU 闭合的影响。总的来说，这项工作将验证 LFLI US 是一种安全、便携且经济有效的慢性伤口治疗方法。这很重要，因为新 迫切需要伤口处理的治疗方法和改进的临床范例。从长远来看， 我们的研究结果可能有助于在护理环境中开发个性化伤口治疗方案。