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: 10480779
• 负责人: Sarah Keim
• 金额: $ 40.05万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480779
• 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 (ASD) 儿童最流行的补充产品之一，其益处的轶事证据和一些小型随机对照试验表明，脂肪酸补充剂可以改善外化行为。由于没有批准的药物可以治疗自闭症谱系障碍的核心症状，善意的父母正在寻求任何可能帮助他们的孩子的产品。这意味着，在没有任何关于其功能、作用机制、有效剂量或利弊的证据基础的情况下，向儿童提供脂肪酸补充剂。非处方 (OTC) 脂肪酸补充剂很丰富，由不同的脂肪酸成分组成，并且通常含有其他成分。我们小组和其他人的最新证据表明，与其他配方相比，补充 DHA、EPA 和 GLA（“Omega 3-6”）的鱼油和琉璃苣油组合特别有前景。在启动严格、全面的疗效试验之前，迫切需要评估 Omega 3-6 的最佳剂量以及与 ASD 症状相关的生理相关生物特征的变化。我们的目标是评估较高剂量的 Omega 3-6 对预先指定的生物特征的影响 我们的总体假设是，Omega 3-6 的最佳剂量将以与 ASD 相关行为的改善相关的方式改变生物特征。该提案的 R61 阶段将测试以下假设：Omega 3-6 将使一种或多种炎症标志物 IL-1β、IL-2 和 IFNγ 产生临床显着降低（改善），并且我们的更高剂量将证明生物利用度、安全性和耐受性。该提案的 R33 阶段将测试以下假设：对生物特征的影响与 Omega 3-6 剂量相关，可以在新的患者样本中复制，并且关键炎症标志物的变化与补充后的核心 ASD 症状相关。完成这个拟议的两阶段项目后，我们希望确定 Omega 3-6 对炎症以及随后对儿童 ASD 症状发挥作用的最佳剂量范围。这些结果预计将产生重要的积极影响，为评估 Omega 3-6 对 ASD 症状改善效果的全面功效试验奠定必要的基础。

项目成果

Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder.

• DOI: 10.1007/s10803-021-05396-9
• 发表时间: 2022-12
• 期刊: JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
• 影响因子: 3.9
• 作者: Keim, Sarah A.;Jude, Abigail;Smith, Katie;Khan, Aiman Q.;Coury, Daniel L.;Rausch, Joseph;Udaipuria, Shivika;Norris, Megan;Bartram, Lindsay R.;Narayanan, Anita R.;Rogers, Lynette K.
• 通讯作者: Rogers, Lynette K.