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

项目总结/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），以测试低频率，低- 高强度（LFLI）超声（US）对慢性伤口愈合和健康相关生活质量（HRQOL）的影响 统计学置信度（α < 0.05，功效> 0.90，n=60 VU，n=60 DU）。我们的方法结合了这种积极的 在整个治疗周期中，通过对伤口血流动力学进行无创诊断监测进行治疗，以及 包括分析营养状况和炎症对伤口闭合的影响。有几 这项工作的创新之处。具体来说，（1）我们的轻量级，电池供电的施用器是第一个 潜在的可穿戴超声伤口治疗设备，其可以安全地应用延长的时间段。（二） 施用器积极促进愈合，这是从根本上不同于商业超声系统 只切除坏死组织(3)我们的方法将LFLI US暴露与伤口变化联系起来 血液动力学和HRQOL，这有可能实现个性化医疗。(4)我们分析 患者的营养和全身炎症状态可以通过识别 最有可能从LFLI US治疗中获益的患者。(5)我们的方法结合了疾病特异性 和HRQOL的通用测量，这是治疗性超声RCT所独有的。 我们的低频、低强度（20 kHz，<100 mW/cm 2空间峰-时峰）便携式超声 施用器是安全的并且临床上实用的伤口治疗。领域 重量轻（<25 g）， 我们的US设备的参数先前针对静脉溃疡进行了优化，我们最近的三个试点临床试验 人体研究（VU：n=20，n=25; DU：n=10）表明，我们的治疗使愈合率提高了15%， 与假治疗相比。因此，我们预计，我们的治疗将加速关闭 我们假设（1）LFLI US将改善一般和疾病特异性HRQOL （2）LFLI US将激活伤口和周围微血管的有益变化 组织，和（3）营养不良和高水平炎症的个体将延迟伤口愈合。 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，通用和疾病特异性HRQOL作为次要终点。(2)监测 使用非侵入性光学方法研究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、经济高效的慢性伤口治疗方法。这一点很重要，因为新 迫切需要用于伤口处理的治疗和改进的临床范例。从长远来看， 我们的研究结果可能使个性化的伤口治疗方案的发展，在整个护理设置。

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.