Fatty acid supplements alter biological signatures in children with Autism Spectrum Disorder

脂肪酸补充剂改变自闭症谱系障碍儿童的生物特征

• 批准号: 10266170
• 负责人: Sarah Keim
• 金额: $ 37.69万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10266170
• 关键词: Adverse event; Affect; Age; Anti-Inflammatory Agents; Behavior Disorders; Biological; Biological Availability; Child; Clinical; Conflict (Psychology); Consumption; Data; Diagnosis; Docosahexaenoic Acids; Docosahexaenoic acid supplementation; Dose; Eicosapentaenoic Acid; Erythrocytes; Family; Fatty Acids; Fish Oils; Formulation; Foundations; Future; Goals; Inflammation; Infrastructure; Interferon Type II; Interleukin-1 beta; Interleukin-2; Lifestyle-related condition; Natural Products; Obesity; Omega-3 Fatty Acids; Outcome; Parents; Participant; Pathway interactions; Patients; Personal Satisfaction; Pharmaceutical Preparations; Phase; Physiological; Plant Extracts; Plasma; Population; Property; Psyche structure; Publishing; Quality of life; Randomized; Reporting; Research; Research Personnel; Safety; Sampling; Specific qualifier value; Supplementation; Symptoms; Testing; Variant; Vitamins; Weight; autism spectrum disorder; autistic children; base; borage oil; clinical research site; clinically significant; comorbidity; design; dietary supplements; dosage; effective therapy; efficacy trial; evidence base; externalizing behavior; fatty acid supplementation; gamma-Linolenic Acid; gastrointestinal; inflammatory marker; physical symptom; primary endpoint; recruit; stem; symptomatic improvement

ABSTRACT Fatty acid supplements are among the most popular complementary products consumed by children with Autism Spectrum Disorder (ASD), driven by anecdotal evidence of benefit and a few small RCTs that demonstrated improvements in externalizing behaviors. Because no approved drugs exist to treat the core symptoms of ASD, well-intentioned parents are reaching for any product that may help their child. The implications are that fatty acid supplements are given to children without any evidence base as to their function, mechanism of action, effective dose, or benefits versus harms. Over-the-counter (OTC) fatty acid supplements are plentiful and consist of varying fatty acid compositions and often contain other ingredients. Recent evidence from our group and others suggest a combination of fish and borage oils providing supplementation of DHA, EPA and GLA (“Omega 3-6”) is particularly promising compared to other formulations. A critical need exists to evaluate Omega 3-6 for optimal dosing and changes in a physiologically relevant biological signature related to ASD symptoms, before a rigorous, full-scale efficacy trial can be launched. Our objective is to evaluate the effects of higher doses of Omega 3-6 on pre-specified biological signatures Our overall hypothesis is that optimal dosing of Omega 3-6 will alter biological signatures in a manner that correlates with improvements in ASD-related behaviors. The R61 phase of this proposal will test the hypothesis that Omega 3-6 will produce a clinically-significant reduction (improvement) in one or more the inflammatory markers IL-1β, IL-2, and IFNγ and our higher doses will demonstrate bioavailability, safety, and tolerability. The R33 phase of this proposal will test the hypothesis that the impact on biological signatures correlates with Omega 3-6 dose, can be replicated in a new sample of patients, and the change in key inflammatory marker(s) are correlated with core ASD symptoms after supplementation. Upon completion of this proposed 2-phase project, we expect to have identified an optimal dosing range for which Omega 3-6 exerts its effect on inflammation and, subsequently, on ASD symptoms in children. Such results are expected to have an important positive impact by laying the necessary groundwork for a full-scale efficacy trial to evaluate the effect of Omega 3-6 on ASD symptom improvement.

抽象的 脂肪酸补充剂是自闭症谱系障碍儿童消耗的最受欢迎的完整产品之一，其福利证据和一些小型RCT驱动，这些证据表现出了外部化行为的改善。由于没有批准的药物来治疗ASD的核心症状，因此善意的父母正在触发任何可能帮助孩子的产品。含义是给儿童提供脂肪酸补充剂，而没有任何证据基础，其功能，作用机理，有效剂量或益处与危害。非处方（OTC）脂肪酸补充剂丰富，包括不同的脂肪酸组成，通常含有其他含量。与其他配方相比，我们小组和其他人的最新证据表明，与其他配方相比，提供了补充DHA，EPA和GLA（“ Omega 3-6”）的鱼类和筛查油（“ Omega 3-6”）是特别有希望的。在可以启动严格的，全尺度的有效性试验之前，对评估与ASD症状相关的物理相关生物学签名的最佳剂量和变化的欧米茄3-6的关键需求。我们的目标是评估较高剂量的Omega 3-6对预先指定的生物学特征的影响。我们的总体假设是，Omega 3-6的最佳剂量会以与ASD相关行为的改善相关的方式改变生物学特征。该提案的R61阶段将检验以下假设：Omega 3-6将在一个或多个炎症标志物IL-1β，IL-2和IFNγ和IFNγ和我们的较高剂量中产生临床意义的降低（改善），将表现出生物可用性，安全性和耐受性。该提案的R33阶段将检验以下假设：对生物学特征的影响与欧米茄3-6剂量相关，可以在新的患者样本中复制，并且密钥炎症标记物的变化与补充后的核心ASD症状相关。该提议的2阶段项目完成后，我们预计将确定一个最佳的给药范围，欧米茄3-6对感染产生了影响，随后对儿童的ASD症状进行了影响。预计通过为全面有效试验奠定必要的基础，以评估欧米茄3-6对ASD符号改进的影响，预计将产生重要的积极影响。