Colorado: Testing Longitudinal Outcome Measures and Improving Minority Participation in Fragile X FORWARD

科罗拉多州：测试纵向结果衡量标准并提高少数族裔对 Fragile X FORWARD 的参与

• 批准号: 9322179
• 负责人: Nicole Renee Tartaglia
• 金额: $ 10万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9322179
• 关键词: Colorado; Testing; Longitudinal; Outcome; Measures

 DESCRIPTION (provided by applicant): Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder with an estimated frequency of about 1:4000-5000, affecting all racial and ethnic groups worldwide. Enormous progress in basic and translational FXS research has identified many neuronal targets and allowed early clinical trials of new treatments targeted to the underlying disease. A number of these agents have shown signal for benefit in open-label and early phase trials, but it has been challenging to meet primary behavioral outcomes in larger phase 2b and 3 trials, due to multiple complex issues including dosing age of subjects, length of treatment, placebo effects, and primary outcome off target for drug effect. A significant problem has been poor availability of biomarkers and well-validated cognitive and other objective outcome measures that do not rely on parent report. Further, very long-term treatment over years, a time frame over which placebo controls are not possible, will be necessary to show changes in the trajectory of disease. In order to know whether the disease trajectory has been changed, it will be CRITICAL to have detailed longitudinal phenotyping including cognitive, adaptive, language, motor, behavioral, social, and quality of life on a large cohort of individuals with FXS, in order to define the naturl history of the disease for future comparison in long-term intervention studies. The FORWARD longitudinal database tracks health, behavior and social issues including 3 standardized measures of behavior and social function in a large cohort of individuals with FXS but lacks good consistent cognitive and adaptive data. Given the infrastructure already present, the FORWARD project is the only currently plausible place to collect the necessary detailed longitudinal phenotyping. Thus, through this application, focused on both enhanced measurement and participation, we plan to collaborate with other Component C sites to enhance the cohort size in which we will collect a comprehensive core battery of outcome measures yearly for a minimum of 3 years to begin to define the longitudinal trajectory of all aspects of the FXS phenotype (Aim 1). At the Denver site we will also collect pilot data longitudinally for new outcome measures addressing areas of need in FXS (Aim 2): a direct measure of social interaction usable across the lifespan (Autism Screening Instrument for Educational Planning-Interaction), efficient assessment of adaptive functioning (Pediatric Evaluation of Disability Inventory-Computer Adaptive Test), detailed tracking of ADHD symptoms across the lifespan (Conners ADHD rating scales), and an efficient battery evaluating motor skills (Fragile X Short Motor Battery). Finally, we will implement plans to improve collection of this data from underrepresented minorities and adults with FXS through outreach activities and collaboration with the Colorado Dept of Health (Aim 3). Analysis plans for data will be reviewed and modified by experts in FXS outcomes research and CDC partners. Results will be disseminated to stakeholders including the FXCRC, NFXF, FXS Community Support Networks, FXS families, other researchers and CDC project partners.

 描述（由申请人提供）：脆性 X 综合征 (FXS) 是自闭症残疾和谱系障碍的最常见遗传原因，估计频率约为 1:4000-5000，影响全世界所有种族和族裔群体。 FXS 转化研究已确定了许多神经元靶标，并允许针对潜在疾病进行新疗法的早期临床试验，其中许多药物已在开放标签和早期试验中显示出有益的信号，但它一直没有进展。由于多种复杂的问题，包括受试者的给药年龄、治疗时间、安慰剂效应以及药物作用的主要结果偏离目标，在更大规模的 2b 期和 3 期试验中实现主要行为结果具有挑战性。一个重要的问题是生物标志物的可用性较差。此外，需要经过充分验证的认知和其他客观结果测量，这些测量不依赖于父母的报告。此外，需要进行多年的长期治疗，在这个时间范围内不可能进行安慰剂对照，以显示疾病轨迹的变化。以便了解疾病轨迹是否有。已经改变，对一大群 FXS 患者进行详细的纵向表型分析（包括认知、适应性、语言、运动、行为、社交和生活质量）至关重要，以便确定该疾病的自然病史。 FORWARD 纵向数据库跟踪大量 FXS 患者的健康、行为和社会问题，包括 3 项标准化的行为和社会功能测量，但鉴于已有的基础设施，缺乏良好的一致的认知和适应性数据。目前， FORWARD 项目是目前唯一可能收集必要的详细纵向表型分析的地方，因此，通过该应用程序，重点关注增强的测量和参与，我们计划与其他组件 C 站点合作，以扩大我们将收集的队列规模。每年至少 3 年进行全面的核心结果测量，开始定义 FXS 表型所有方面的纵向轨迹（目标 1）。在丹佛站点，我们还将纵向收集试点数据，以用于解决以下领域的新结果测量。需要 FXS （目标 2）：可用于整个生命周期的社会互动的直接衡量标准（教育规划互动自闭症筛查工具），适应性功能的有效评估（残疾量表的儿科评估 - 计算机适应性测试），整个生命周期中 ADHD 症状的详细跟踪最后，我们将实施计划来改进对代表性不足的少数群体的数据收集。通过外展活动以及与科罗拉多州卫生部的合作，了解患有 FXS 的成年人（目标 3）。 由 FXS 结果研究专家和 CDC 合作伙伴进行审查和修改。结果将分发给利益相关者，包括 FXCRC、NFXF、FXS 社区支持网络、FXS 家庭、其他研究人员和 CDC 项目合作伙伴。