Development of an Ecological Momentary Assessment Outcome Measure for Down Syndrome Clinical Trials

唐氏综合症临床试验生态瞬时评估结果测量的开发

• 批准号: 10295716
• 负责人: DAVID R HESSL
• 金额: $ 43.18万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10295716
• 关键词: Adaptive Behaviors; Adolescent; Adult; Age; Animal Model; Animals; Assessment tool; Attention; Attention deficit hyperactivity disorder; Award; Behavior; Behavior assessment; Behavioral; Brain; Caregivers; Cellular Phone; Child; Climacteric; Clinic; Clinical; Clinical Trials; Cognitive; Collaborations; Collection; Controlled Clinical Trials; Cross-Over Trials; Data; Dementia; Detection; Development; Double-Blind Method; Down Syndrome; Ecological momentary assessment; Equipment and supply inventories; Evaluation; Executive Dysfunction; Expectancy; Failure; Fragile X Syndrome; Functional disorder; Funding; Future; Goals; Grant; Home; Home environment; Individual; Intellectual functioning disability; Intervention; Interview; Investigation; Laboratories; Life; Liquid substance; Longevity; Measurement; Measures; Memory; Methods; Neurobiology; Neurodevelopmental Disorder; Outcome Measure; Participant; Patients; Persons; Pharmaceutical Preparations; Phenotype; Placebo Effect; Placebos; Population; Predisposition; Problem behavior; Process; Questionnaires; Randomized; Research; Research Personnel; Respondent; Risk; Ritalin; Sampling; Short-Term Memory; Specialist; System; Testing; Time; Training; Translational Research; United States National Institutes of Health; Validation; Validity and Reliability; base; behavior measurement; behavior rating scale; behavioral construct; clinical outcome measures; clinical trial readiness; cognitive change; cognitive performance; cognitive testing; cohort; comorbidity; daily functioning; design; educational atmosphere; executive function; flexibility; improved; innovation; member; mental age; novel; performance based measurement; preclinical study; smartphone based assessment; success; teacher; tool; treatment comparison; treatment duration; treatment response; working group

Abstract There is a growing translational research effort to understand the brain mechanisms of dysfunction in neurodevelopmental disorders including Down syndrome (DS) and other conditions that cause intellectual and developmental disability (IDD). Targeted treatments under development, often supported by animal studies, have the potential to normalize, or at least substantially mitigate, the neurobiological, cognitive, and behavioral problems associated with DS. However, several controlled clinical trials focused on DS and other IDDs (such as fragile X syndrome) in the past decade have been completed with limited success. Although the medications may actually be ineffective or inadequately provide clinical benefit, other explanations for trial failures include limited brain plasticity in the adults or adolescents studied, robust placebo effects that may obscure true benefits of active drug, and outcome measures that are inadequately sensitive to changes occurring in daily life. Optimization of ecologically valid, reliable and sensitive outcome measures for these conditions will facilitate the evaluation and identification of effective and clinically meaningful interventions. Executive dysfunction (ED), spanning processes and behaviors of planning and goal-directed behavior, cognitive flexibility, working memory, inhibitory control, and several forms of attention, has been emphasized by NIH DS working groups and other investigators as a key domain to target in trials. ED is a key component of the cognitive phenotype of DS, is predictive of limitations in adaptive functioning, and may be associated with risk for later dementia in this population. The primary aim of this project is to refine and develop the preliminary feasibility, reliability and validity of a smartphone-based electronic Ecological Momentary Assessment (eEMA) tool (iBehavior) for caregiver and teacher ratings of behaviors associated with ED in the daily lives (home and classroom environments) of children and adolescents with DS and IDD. The second aim of the project is to utilize the tool in the context of an already planned and funded (R01HD076189) double-blind placebo- controlled crossover trial of extended release methylphenidate in children and adolescents with DS and other forms of IDD with comorbid ADHD. This aim will determine iBehavior’s sensitivity to treatment and relative susceptibility to placebo effects compared to other rating scales and cognitive tests. The empirical validation of an eEMA app appropriate for use as an outcome measure in future DS trials will provide a technologically novel method for use in the home and classroom setting that has the potential to detect treatment-related changes in daily life, changes that may not be adequately captured by laboratory tests or retrospective caregiver questionnaires and interviews.

抽象的 人们越来越多地进行转化研究来了解大脑功能障碍的机制 神经发育障碍，包括唐氏综合症 (DS) 和其他导致智力和智力障碍的疾病 发育障碍（IDD）的靶向治疗正在开发中，通常得到动物研究的支持， 有可能使神经生物学、认知和行为正常化或至少显着减轻 然而，一些对照临床试验的重点是 DS 和其他 IDD（例如 脆性 X 综合征）在过去十年中已完成，但取得了有限的成功。 药物实际上可能无效或不能充分提供临床益处，试验的其他解释 失败包括所研究的成年人或青少年的大脑可塑性有限，强大的安慰剂效应可能会 掩盖了活性药物的真正益处，以及对变化不够敏感的结果指标 优化这些在日常生活中发生的生态有效、可靠和敏感的结果措施。 条件将有助于评估和确定有效且具有临床意义的干预措施。 执行功能障碍（ED），跨越计划和目标导向行为的过程和行为， 认知灵活性、工作记忆、抑制控制和几种形式的注意力都得到了强调 NIH DS 工作组和其他研究人员将 ED 视为试验的关键组成部分。 DS 的认知表型可以预测适应性功能的局限性，并且可能与 该项目的主要目的是完善和发展初步的痴呆症风险。 基于智能手机的电子生态瞬时评估（eEMA）的可行性、可靠性和有效性 工具 (iBehavior)，用于照顾者和教师对日常生活（家庭和家庭）中与 ED 相关的行为进行评分 该项目的第二个目标是： 在已经计划和资助的（R01HD076189）双盲安慰剂的背景下利用该工具 哌醋甲酯缓释剂用于患有 DS 和其他疾病的儿童和青少年的对照交叉试验 该目标将确定 iBehavior 对治疗和相关疾病的敏感性。 与其他评分量表和认知测试相比对安慰剂效应的敏感性。 适合在未来 DS 试验中用作结果测量的 eEMA 应用程序将提供技术上的支持 在家庭和教室环境中使用的新颖方法，有可能检测与治疗相关的 日常生活中的变化，实验室测试或回顾性可能无法充分捕获的变化 问卷调查和访谈。