Clinical & metabolic effects of altering n-3 & n-6 fatty acids in migraine (RCT)

临床

• 批准号: 8632138
• 负责人: JOHN DOUGLAS MANN
• 金额: $ 66.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632138
• 关键词: Address; Adherence; Adult; Adverse effects; Affect; Agonist; American; Analgesics; Arachidonic Acids; Biochemical; Biochemical Pathway; Chronic Daily Headaches; Chronic disabling pain; Clinical; Clinical Research; Control Groups; Controlled Clinical Trials; Data; Diet; Diet Modification; Dietary Assessment; Dietary Intervention; Dietary Practices; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids; Feasibility Studies; Food; Frequencies; Funding; Goals; Headache; Health Care Costs; Hour; Human; Individual; Intake; Intervention; Lead; Link; Linoleic Acids; Measures; Metabolic; Migraine; Modeling; Modification; N-3 polyunsaturated fatty acid; National Center for Complementary and Integrative Health; Neurons; Neuropeptides; Nociception; Omega-3 Fatty Acids; Outcome; Pain; Pain Disorder; Pain management; Participant; Pathogenesis; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Polyunsaturated Fatty Acids; Prevention; Public Health; Quality of life; Randomized; Research; Single-Blind Study; Solid; Symptoms; Syndrome; TRPV1 gene; Testing; Tissues; Work; arm; base; capsaicin receptor; chronic pain; clinical effect; clinical efficacy; conventional therapy; cost; design; diaries; dietary control; experience; improved; in vivo; innovation; pilot trial; public health relevance; receptor; response; treatment as usual

Episodic migraine is a debilitating chronic pain condition afflicting 12% of American adults. Current conventional treatments rely on medications that provide limited or transient relief, target symptoms rather than the underlying causes of pain, and are associated with significant side effects and costs. It is therefore essential to investigate non-pharmacologic approaches to conventional headache treatments. Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) regulate multiple pain-related biochemical pathways. Controlled clinical trials investigating pain modulation in response to dietary changes while exploring relevant mechanisms of action in humans are lacking. In a recent feasibility study in patients with chronic daily headache (CDH), we found that targeted PUFA modifications - increased dietary n-3 EPA+DHA with reduced n-6 linoleic acid (LA) intake - altered circulating endovanilloids, while reducing headache frequency and improving quality of life. These findings support our proposed model in which diet-induced alterations in endovanilloids modulate TRPV1 activity in vivo, leading to important implications for migraine and chronic pain in general. However, whether a reduction in dietary LA is required to elicit the observed metabolic and clinical benefits of raising n-3 PUFA intake is unknown. The goal of this research is to assess whether dietary PUFA modifications designed to increase tissue n-3 EPA and DHA, with or without concurrent reduction in n-6 LA, can result in predicted changes in circulating endovanilloids and improvement in headache-related clinical outcomes. The proposed 3-arm, 20-week, randomized, controlled, single-blind trial, with 51 subjects in each group, includes a 4-week baseline of usual care, followed by randomization to one of three 16-week dietary interventions plus usual care: 1) a High n-3 EPA+DHA, Low n-6 LA intervention (Diet A); 2) a High n-3 EPA+DHA, High n-6 LA intervention (Diet B); or 3) a control intervention with average U.S. intakes (Low n-3, High n-6, Diet C). Specific aims are: 1) To assess the efficacy of the dietary interventions in inducing the predicted changes in circulating PUFA endovanilloid derivatives; 2) To compare the clinical effects in migraine specific outcomes of two 16-week analgesic dietary interventions with each other and a control diet; 3) To test, in an exploratory manner, our model of the proposed causal chain linking changes in n-3 and n-6 PUFAs, their endovanilloid derivatives, and headache clinical endpoints. This proposal utilizes an innovative design and hypotheses to address current NCCAM research funding priorities, by examining clinical efficacy and underlying mechanisms of a promising dietary manipulation with the distinct potential for high impact in terms of ameliorating a chronic, disabling pain disorder.

发作性偏头痛是一种使人衰弱的慢性疼痛状况，困扰着12%的美国成年人。电流 传统的治疗依赖于提供有限或短暂缓解的药物，靶向症状，而不是 疼痛的根本原因，并与显着的副作用和成本。因此 研究传统头痛治疗的非药物方法至关重要。欧米茄-6（n-6） 和ω-3（n-3）多不饱和脂肪酸（PUFA）调节多种疼痛相关的生物化学途径。 对照临床试验，研究饮食变化对疼痛的调节作用，同时探索相关的 在人体内缺乏作用机制。 在最近的一项针对慢性每日头痛（CDH）患者的可行性研究中，我们发现靶向PUFA 修改-增加膳食n-3 EPA+DHA，减少n-6亚油酸（LA）摄入量-改变 循环内香草素，同时减少头痛频率和改善生活质量。这些发现 支持我们提出的模型，其中饮食诱导的内香草素改变调节TRPV 1活性， 体内，导致偏头痛和一般慢性疼痛的重要影响。然而，无论减少 在饮食中，需要LA来引起观察到的提高n-3 PUFA摄入量的代谢和临床益处， 未知 这项研究的目的是评估是否饮食PUFA修改旨在增加组织 n-3 EPA和DHA，伴随或不伴随n-6 LA的减少，可导致循环中的预期变化。 内香草素和改善头痛相关的临床结果。拟议的3臂，20周， 一项随机、对照、单盲试验，每组51例受试者，包括4周的常规基线 护理，然后随机分为三个16周的饮食干预加常规护理之一： EPA+DHA，低n-6 LA干预（饮食A）; 2）高n-3 EPA+DHA，高n-6 LA干预（饮食B）;或3） 美国平均摄入量的对照干预（低n-3，高n-6，饮食C）。 具体目标是：1）评估饮食干预在诱导预测的 循环PUFA香草醛衍生物的变化; 2）比较偏头痛特异性 两个为期16周的止痛饮食干预的结果与对方和对照饮食; 3）为了测试，在一个 探索性的方式，我们提出的因果链连接的n-3和n-6多不饱和脂肪酸的变化模型，其 内香草素衍生物和头痛临床终点。 这项建议利用创新的设计和假设，以解决目前的NCCAM研究 资金优先事项，通过检查临床疗效和潜在的机制，有前途的饮食 在改善慢性致残性疼痛方面具有明显高影响潜力的操作 disorder.