BACKGROUND This trial addresses the global problem of chronic venous leg ulcers (CVLUs), wounds that cause significant infirmity for an estimated 9.7 million people annually, mainly older adults with comorbidities. Advanced therapies are needed because standard topical therapies are often ineffective or yield only short-term wound healing. Thus, we are testing a new oral therapy containing the bioactive elements of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for targeting and reducing the high numbers of activated polymorphonuclear leukocytes (PMN) in wound microenvironments that keep CVLUs "trapped" in a chronic inflammatory state. METHODS This double-blind RCT will include 248 eligible adults ≥ 55 years of age with CVLUs receiving standard care at a large Midwest outpatient wound clinic. Participants are randomized to two groups: 12 weeks of daily oral therapy with EPA + DHA (1.87 g/day of EPA + 1.0 g/day of DHA) or daily oral therapy with placebo. At 0, 4, 8, and 12 weeks, across the two groups, we are pursuing three specific aims: Aim 1. Compare levels of EPA + DHA-derived lipid mediators, and inflammatory cytokines in blood and wound fluid; Subaim 1a. Compare inflammatory cytokine gene expression by PMNs in blood; Aim 2. Compare PMN activation in blood and wound fluid, and PMN-derived protease levels in wound fluid; Aim 3. Compare reduction in wound area, controlling for factors known to impact healing, and determine relationships with lipid mediators, cytokines, and PMN activation. Subaim 3a. Compare frequency of CVLU recurrence and levels of study variables in blood between the randomly assigned two subgroups (continuing EPA + DHA therapy versus placebo therapy beyond week 12) within the EPA + DHA group with healed CVLUs after 3 months of therapy. Subaim 3b. Compare symptoms of pain at all time points and quality of life at first and last time points across the two groups and two subgroups. DISCUSSION This trial will provide new evidence about the effectiveness of EPA + DHA oral therapy to target and reduce excessive PMN activation systemically and locally in patients with CVLUs. If effective, this therapy may facilitate healing and thus be a new adjunct treatment for CVLUs in the aging population. TRIAL REGISTRATION ClinicalTrials.gov, NCT03576989; Registered on 13 June 2018.

中文翻译：

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omega-3脂肪酸口服疗法对老年人慢性静脉腿溃疡愈合的影响：一项针对随机对照单中心试验的研究方案。

背景技术该试验解决了慢性静脉腿溃疡（CVLUs）的全球性问题，这种伤口每年导致估计约970万人的严重疾病，主要是合并症的老年人。需要先进的疗法，因为标准的局部疗法通常无效或只能短期伤口愈合。因此，我们正在测试一种新的口服疗法，该疗法包含鱼油，二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的生物活性成分，可靶向并减少伤口微环境中活化的多形核白细胞（PMN）的数量，从而保持CVLUs不变。被困在慢性炎症状态。方法该双盲RCT将包括248名≥55岁的合格成年人，他们在大型中西部门诊伤口诊所接受CVLU的标准护理。参加者随机分为两组：每日EPA + DHA口服治疗12周（1.87 g /天EPA + 1.0 g /天DHA）或每日安慰剂口服治疗。在两组的第0、4、8和12周，我们追求三个具体目标：目的1.比较EPA + DHA衍生的脂质介体的水平以及血液和创面液中的炎性细胞因子；Subaim 1a。比较血液中PMN的炎性细胞因子基因表达；目的2.比较血液和伤口液中PMN的活化，以及伤口液中PMN衍生的蛋白酶水平；目的3.比较伤口面积的减少，控制已知影响愈合的因素，并确定与脂质介质，细胞因子和PMN活化的关系。Subaim 3a。在治疗3个月后，比较CVLU愈合后的EPA + DHA组中随机分配的两个亚组（连续EPA + DHA治疗与安慰剂治疗之间超过12周）的CVLU复发频率和血液中的研究变量水平。Subaim 3b。比较两组和两个亚组在所有时间点的疼痛症状以及第一时间和最后一个时间点的生活质量。讨论本试验将提供有关EPA + DHA口服疗法有效靶向和减少CVLU患者全身和局部过度PMN激活的有效性的新证据。如果有效，该疗法可促进愈合，因此是老龄化人群中CVLU的新辅助疗法。试验注册ClinicalTrials.gov，NCT03576989；2018年6月13日注册。