A Dried Blood Spot Companion Diagnostic to Measure Neuroendocrine Changes in ADHD.

干血斑伴随诊断可测量 ADHD 的神经内分泌变化。

• 批准号: 10091652
• 负责人: Ekaterina A Placzek
• 金额: $ 5.5万
• 依托单位: ZRT LABORATORY, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2021-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091652
• 关键词: Address; Age; Allopregnanolone; Alternative Therapies; Attention deficit hyperactivity disorder; Bedside Testings; Biological; Biological Assay; Blood; Blood specimen; Child; Clinical; Clinical Research; Collection; Complement; Detection; Development; Disease; Disease remission; Evaluation; Future; Glutamates; Goals; Gold; Health Sciences; Healthcare Industry; Heterogeneity; Home environment; Hyperactive behavior; Impulsivity; Individual; Knowledge; Kynurenine; Laboratories; Liquid Chromatography; Liquid substance; Measures; Methods; Modality; Monitor; Nature; Neurobiology; Neurodevelopmental Disorder; Neurosecretory Systems; Neurotransmitters; Oregon; Outcome; Pathology; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Population Control; Prediction of Response to Therapy; Process; Questionnaires; Randomized; Recovery; Reproducibility; Research; Sampling; Sensitivity and Specificity; Serotonin; Small Business Innovation Research Grant; Source; Spottings; Steroids; Symptoms; Testing; Treatment Protocols; Treatment outcome; Universities; Urine; Validation; Whole Blood; Work; alternative treatment; analytical method; base; clinically actionable; clinically relevant; companion diagnostics; control trial; cost; design; developmental disease; dietary supplements; evidence base; flexibility; gamma-Aminobutyric Acid; inattention; minimally invasive; neurosteroids; pediatric patients; personalized medicine; point of care; primary outcome; prototype; reduce symptoms; research clinical testing; response; side effect; standard of care; success; symptomatology; tandem mass spectrometry; tool; treatment adherence; treatment response; urinary

REVISED ABSTRACT Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder marked by inattention, hyperactivity and impulsivity. Stimulant therapies can be effective for alleviating ADHD symptoms; however, due to neurobiological heterogeneity of ADHD, some patients are non-responders, or develop undesirable side effects. This creates a process of trial-and-error in the clinical pursuit of alternative treatment options. Currently there are no widely utilized laboratory tests that measure clinically actionable neuroendocrine analytes in ADHD that can provide adequate prediction of treatment success and remission. This project will develop a companion diagnostic for ADHD to complement existing symptom evaluation questionnaires, which are indirect measures of treatment outcome. The proposed companion diagnostic encompasses developing a clinical test for neuroendocrine molecules – GABA, allopregnanolone, glutamate, serotonin and kynurenine analyzed in dried blood spot (DBS) due to its minimally-invasive nature. We will use pre-existing whole blood samples from children with ADHD collected as part of an active randomized control trial by a team of academic collaborators at Oregon Health & Science University to evaluate and confirm dysregulated neuroendocrine tone in ADHD. Specific aims: 1. A) Develop and validate an analytical assay for GABA and allopregnanolone in DBS. We will determine analytical parameters, including linearity, recovery, precision, etc., and confirm accuracy by comparing DBS to liquid blood analysis, which is the currently accepted gold standard method. 1. B) Incorporate glutamate, serotonin and kynurenine analytes for simultaneous analysis. 2. Evaluate the performance of the clinical test using DBS samples from medication-free pediatric patients with ADHD. Completion of these aims will serve as proof-of-concept for a fully validated DBS test for baseline (no treatment) levels of GABA, allopregnanolone, glutamate, serotonin and kynurenine in ADHD. This will establish the basis for Phase II, developing a comprehensive clinical study that will examine the changes in neuroendocrine parameters in response to stimulants, non-stimulants and nutritional supplements used in ADHD.

修订后的摘要 注意力缺陷多动障碍（ADHD）是一种常见的神经发育障碍，其特征是注意力不集中、多动和冲动。兴奋剂疗法可有效缓解多动症症状；然而，由于多动症的神经生物学异质性，一些患者没有反应，或者出现不良副作用。这在临床寻求替代治疗方案中创造了一个反复试验的过程。目前，还没有广泛使用的实验室测试来测量 ADHD 中临床上可行的神经内分泌分析物，从而可以充分预测治疗成功和缓解。该项目将开发一种 ADHD 伴随诊断，以补充现有的症状评估调查问卷，这些调查问卷是治疗结果的间接衡量标准。拟议的伴随诊断包括开发神经内分泌分子的临床测试——GABA、四氢孕酮、谷氨酸、血清素和犬尿氨酸，由于其微创性质，在干血斑 (DBS) 中进行分析。我们将使用来自多动症儿童的现有全血样本，作为俄勒冈健康与科学大学学术合作者团队主动随机对照试验的一部分收集，以评估和确认多动症患者的神经内分泌失调。具体目标： 1. A) 开发并验证 DBS 中 GABA 和四氢孕酮的分析测定方法。我们将确定分析参数，包括线性、回收率、精密度等，并通过比较 DBS 与液体血液分析（目前公认的金标准方法）来确认准确性。 1. B) 合并谷氨酸、血清素和犬尿氨酸分析物以进行同步分析。 2. 使用来自未接受药物治疗的 ADHD 儿科患者的 DBS 样本评估临床测试的性能。 这些目标的完成将作为对 ADHD 中 GABA、四氢孕酮、谷氨酸、血清素和犬尿氨酸的基线（无治疗）水平进行充分验证的 DBS 测试的概念验证。这将为第二阶段奠定基础，开展一项全面的临床研究，检查神经内分泌参数对 ADHD 中使用的兴奋剂、非兴奋剂和营养补充剂的反应变化。