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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.

拟议的研究解决了国家老龄化研究所的使命——增进理解和改善衰老过程中慢性伤口的健康结果。拟议项目的目标是增强了解慢性腿部静脉溃疡 (CVLU) 并为治疗提供循证指导 CVLU，即导致老年人大量发病、残疾、住院甚至死亡的伤口成年人。需要针对 CVLU 的新疗法，因为标准局部疗法通常无效或无效只能短期治愈。与 PA-16-230 一致，即衰老中的不愈合溃疡性伤口，该项目的跨学科团队计划测试一种含有鱼油生物活性元素的口服营养疗法刺激愈合并防止 CVLU 复发。 CVLU 病理学涉及静脉高压和高静脉循环和溃疡中活化的多形核白细胞（PMN）的数量它们分泌过量的蛋白酶，使溃疡长期发炎。该团队之前工作的集体数据支持了这样的组织假设：增加摄入量口服补充剂二十碳五烯酸 (EPA) 和二十二碳六烯酸 (DHA) 将加速 CVLU 通过提高 EPA+DHA 衍生脂质介质的水平并降低促炎细胞因子，从而减少全身和溃疡微环境中的 PMN 激活。这集体结果预计还将缓解 CVLU 相关疼痛并提高生活质量 (QoL)。这随机、双盲研究拟纳入 248 名连续合格的 ≥ 60 岁患有 CVLU 的成年人他们继续在两个大学门诊伤口诊所接受标准护理。参与者将被随机分配分为 2 组：12 周每日口服 EPA+DHA（2.5 克/天 EPA + 0.5 克/天 DHA）或每日口服治疗与安慰剂。在第 0、4、8 和 12 周时，团队将在 2 个组中追求三个具体目标：目标 1。比较血液和 CVLU 液中 EPA+DHA 衍生的脂质介质和炎症细胞因子的水平；苏拜姆 1a.比较血液中 PMN 的炎症细胞因子基因表达；目标 2. 比较 PMN 血液和 CVLU 液中的活化，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。苏拜姆 3a。比较 CVLU 复发频率和研究变量水平 EPA+DHA 组内 2 个亚组之间血液中的 CVLU 已愈合（另外 3 个月后） EPA+DHA 治疗与第 12 周后的安慰剂治疗的比较）。苏拜姆 3b.比较一下疼痛的症状 2 个组和 2 个亚组的第一个和最后一个时间点的时间点和 QoL。研究结果符合预期开发出一种新的低风险辅助口服疗法，以针对并减少 CVLU 患者的过度 PMN 激活。因此，该疗法有望刺激衰老过程中 CVLU 的愈合、阻止复发并改善生活质量。