Impact of Omega-3 Fatty Acid Oral Therapy on Healing of Chronic Venous Leg Ulcers in Older Adults

Omega-3 脂肪酸口服疗法对老年人慢性静脉腿部溃疡愈合的影响

基本信息

批准号：
10399450
负责人：
Jodi Christine McDaniel
金额：
$ 57.68万
依托单位：
OHIO STATE UNIVERSITY
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 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10399450
关键词：
Address Adult Affect Age-Years Aging Area Blood Blood Circulation Cells Chronic Clinic Clinical Cytokine Gene Data Diet Docosahexaenoic Acids Double-Blind Method Eicosapentaenoic Acid Elderly Elements Fish Oils Frequencies Gene Expression Goals Health Health Care Costs Hospitalization Hypertension Inflammatory Intake Knowledge Lead Leg Ulcer Liquid substance Mission Morbidity - disease rate National Institute on Aging Nutrient Omega-3 Fatty Acids Oral Outcome Outpatients Pain Pain quality Participant Patients Peptide Hydrolases Persons Placebos Quality of life Randomized Recurrence Research Rice Risk Science Site Subgroup Testing Time Treatment Cost Ulcer Universities Venous Visit Work chronic ulcer chronic wound cohort comorbidity cytokine disability evidence base experimental study handicapping condition healing improved leukocyte activation lipid mediator migration mortality neutrophil novel therapeutics oral supplementation pain symptom prevent skin ulcer standard care targeted treatment western diet wound wound healing

项目摘要

The proposed research addresses a mission of the National Institute on Aging – to develop understanding and improve health outcomes of chronic wounds in aging. The goals of the proposed project are to enhance knowledge of chronic venous leg ulcers (CVLUs) and provide evidence-based guidance in the treatment of CVLUs, wounds that cause substantial morbidity, disability, hospitalization, and even mortality among older adults. New therapies for CVLUs are needed because standard topical therapies are often ineffective or yield only short-term healing. Congruent with PA-16-230, Non-healing Ulcerative Wounds in Aging, the project’s interdisciplinary team plans to test an oral nutrient therapy containing the bioactive elements of fish oil to stimulate healing and prevent recurrence of CVLUs. CVLU pathobiology involves venous hypertension and high numbers of activated polymorphonuclear leukocytes (PMNs) in venous circulation and the ulcer microenvironment, where they secrete excessive amounts of proteases that keep ulcers chronically inflamed. Collective data from the team’s previous work support the organizing hypothesis that increasing intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with oral supplementation will expedite CVLU healing and prevent recurrence by raising levels of EPA+DHA-derived lipid mediators and lowering levels of proinflammatory cytokines, thereby reducing PMN activation systemically and in ulcer microenvironments. The collective outcomes are also expected to relieve CVLU-related pain and improve quality of life (QoL). The randomized, double-blind study proposes to include 248 successive eligible adults ≥ 60 years of age with CVLUs who continue to receive standard care at two university out-patient wound clinics. Participants will be randomized to 2 groups: 12 weeks of daily oral therapy with EPA+DHA (2.5 g/d of EPA + 0.5 g/d of DHA) or daily oral therapy with placebo. At 0, 4, 8 and 12 weeks, across the 2 groups, the team will pursue three specific aims: Aim 1. Compare levels of EPA+DHA-derived lipid mediators, and inflammatory cytokines in blood and CVLU fluid; Subaim 1a. Compare inflammatory cytokine gene expression by PMNs in blood; Aim 2. Compare PMN activation in blood and CVLU fluid, and PMN-derived protease levels in CVLU fluid; Aim 3. Compare reduction in wound area, controlling for factors known to affect 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 2 subgroups within the EPA+DHA group with healed CVLUs (after 3 additional months of EPA+DHA therapy versus placebo therapy beyond Week 12). Subaim 3b. Compare the symptom of pain at all time points and QoL at first and last time points across the 2 groups and 2 subgroups. The findings are expected to lead to a new low-risk adjunct oral therapy to target and reduce excessive PMN activation in CVLU patients. As such, the therapy is expected to stimulate healing of CVLUs in aging, deter recurrence and improve QoL.

拟议的研究涉及美国国家老化研究所的使命 - 建立理解和改善衰老中慢性伤口的健康结果。拟议项目的目标是增强了解慢性静脉腿溃疡（CVLUS），并提供基于证据的指导 CVLUS赢得了大量发病率，残疾，住院甚至死亡率的胜利成年人。需要新的CVLU疗法，因为标准局部疗法通常无效或产量只有短期康复。与PA-16-230的一致，衰老中的非愈合溃疡伤口，该项目的跨学科团队计划测试含有鱼油生物活性元素的口服营养疗法刺激愈合并防止CVLUS复发。 CVLU病理生物学涉及静脉高血压和高静脉循环和溃疡中活化的多形核白细胞（PMN）数量微环境，它们的秘密超过了使溃疡长期发炎的蛋白酶的数量。团队先前工作的集体数据支持了组织的假设，即增加摄入量带口服补充的eicosapentaenoic酸（EPA）和二十六烯酸（DHA）将加快CVLU 通过提高EPA+DHA衍生的脂质介质的水平并降低水平，从而康复并防止复发促炎细胞因子，从而在系统和溃疡微环境中降低PMN激活。这预计集体结果还将挽救与CVLU相关的疼痛并改善生活质量（QOL）。随机，双盲研究建议包括248名成功的合格成年人≥60岁的CVLUS 他继续在两个大学门诊逻辑上获得标准护理。参与者将是随机的到2组：EPA + DHA（2.5 g/d的EPA + 0.5 g/d的DHA）或每日口腔治疗的每日12周口服治疗安慰剂。在两个小组中，在0、4、8和12周，团队将追求三个特定目标：AIM 1。比较血液和CVLU液中EPA+DHA衍生的脂质介质的水平以及炎症细胞因子； Subaim 1A。比较血液中PMN的炎性细胞因子基因表达；目标2。比较PMN 血液和CVLU液的激活，以及CVLU液中PMN衍生的蛋白酶水平；目标3。比较减少在伤口区域，控制已知会影响愈合的因素，并确定与脂质介质的关系，细胞因子和PMN激活。 Subaim 3a。比较CVLU复发的频率和研究变量的水平在EPA+DHA组中有加热CVLU的2个亚组之间的血液中（另外3个月后 EPA+DHA疗法与第12周以后的安慰剂疗法与安慰剂疗法）。 Subaim 3b。完全比较疼痛的症状时间点和QOL在两个组和2个亚组的首先和最后一个时间点。期望这些发现导致新的低风险辅助疗法，以靶向和减少CVLU患者的过量PMN激活。因此，预计该疗法将刺激CVLU在衰老中的愈合，确定复发并改善QOL。