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（由适用提供）：脆弱的X综合征（FXS）是最常见的智障和自闭症谱系障碍的遗传原因，估计频率约为1：4000-5000，影响了全球所有种族和种族。基本和翻译FXS研究的巨大进展已经确定了许多神经元靶标，并允许对针对潜在疾病的新疗法进行早期临床试验。这些代理中的许多试剂在开放标签和早期试验中显示了对益处的信号，但是由于多个复杂的问题，包括受试者的给药年龄，安慰剂的长度，安慰剂效应和药物效应目标的主要结果，要在较大阶段2B和3次试验中达到主要行为结果的挑战。一个重大的问题是生物标志物以及不依赖父母报告的认知和其他客观结果指标的可用性差。此外，多年来的长期治疗是不可能的安慰剂控制的时间范围，以显示疾病轨迹的变化是必要的。为了知道疾病轨迹是否已改变，要在大量有FXS的人群上进行详细的纵向表型，包括认知，自适应，语言，运动，运动，行为，社交和生活质量，以定义长期干预研究中未来比较的疾病的自然史。远期纵向数据库跟踪了大量有FXS的人群中的健康，行为和社会问题，包括3种标准化的行为和社会功能指标，但缺乏良好的一致性认知和适应性数据。鉴于已经存在的基础设施，远期项目是当前唯一收集必要详细纵向表型的地方。通过此应用，我们计划与其他组件C站点合作，以增强测量和参与度，以增强队列规模，在其中我们将每年收集最少3年的全面核心核心核心电池，以开始定义FXS现象的各个方面的纵向轨迹（AIM 1）。 a direct measurement 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).最后，我们将通过宣传活动和与科罗拉多州健康部的合作，从代表性不足的少数群体和成年人中收集这些数据的计划（AIM 3）。数据分析计划将 FXS结果研究和CDC合作伙伴的专家进行审查和修改。结果将被传播给FXCRC，NFXF，FXS社区支持网络，FXS家庭，其他研究人员和CDC项目合作伙伴等利益相关者。