PAR-18-953 (ASCOT-DMD)

项目摘要 该应用程序的前提是由肌肉营养不良症的战略优先事项通知 美国国立卫生研究院（NIH）协调委员会（MDCC），并从我们的临床 对Duchenne型肌营养不良症（DMD）认知功能的研究体会。认知健康 是DMD患者生活质量（QoL）的关键决定因素之一。预期寿命的提高， 沿着这一罕见疾病领域令人兴奋的药物开发和药物批准步伐 为治疗DMD的认知症状提供了更广泛的背景。的 临床前的成功可以更快地转化为临床试验， 鲁棒的性能结果（PerfO）的认知措施。在这个应用程序中，我们带来了一个团队， 科学方法，利用Thangarajh博士，亚当斯和Kaat博士的研究专长， 调查NIH认知测验（NIHTB-CB）的强度，作为一项性能- DMD认知功能的结果测量。NIHTB-CB允许连续测量，满足 NIH要求科学严谨性和可重复性，并可扩展用于多地点临床试验， 与不能在临床上以高保真度应用的金标准神经心理学测试不同， 试验设置。建议的具体目标是建立（一）重测信度， NIHTB-CB的实践效果，（ii）使用患者报告的结局指标（PROM）， 确定参与者自我报告的功能、生活质量和症状负担，以及（iii）纵向 使用NIHTB-CB评估认知发展。这项前瞻性纵向研究将评估 46名受试者采用NIHTB-CB、认知特异性PROM和标准化评定量表。的 将在基线、3周（± 1周）和1年时给予NIHTB-CB，以研究 重测可靠性和实践效果，这是FDA批准任何 PerfO措施。创新：该提案首次调查NIHTB-CB是否成立 承诺作为DMD认知的PerfO测量。我们采用团队科学的方法来提高 DMD的认知研究足迹我们研究的完成将提供科学的 在DMD临床试验中采用NIH作为认知的PerfO测量的基本原理。

Project Summary The premise of this application is informed by the strategic priorities of the Muscular Dystrophy Coordinating Committee (MDCC) of the National Institutes of Health (NIH), and from our clinical and research experience on cognition in Duchenne Muscular Dystrophy (DMD). Cognitive health is one of the key determinants of quality-of-life (QoL) in DMD. The improvement in life-expectancy, along with the exciting pace of drug development and drug approval in this rare disease space has provided a backdrop to be more inclusive of treating cognitive symptoms in DMD. The preclinical success can be more rapidly translated to clinical trials by establishing sensitive and robust performance-outcome (PerfO) measures of cognition. In this application, we bring a team science approach, leveraging the research expertise of Drs. Thangarajh, Adams and Kaat to investigate the strength of the NIH Toolbox Cognition Battery (NIHTB-CB), as a performance- outcome measure for cognition in DMD. The NIHTB-CB permits continuity of measurement, fulfills the NIH mandate for scientific rigor and reproducibility, and is scalable for multi-site clinical trials, unlike gold-standard neuropsychological tests which cannot be applied with high fidelity in clinical trial settings. The specific aims of the proposal are to establish the (i) test-retest reliability and practice effects of the NIHTB-CB, (ii) to use patient-reported outcome measures (PROMs) to identify participants’ self-reported function, QoL, and symptom burden, and (iii) to longitudinally assess cognitive development using NIHTB-CB. This prospective, longitudinal study will assess 46 participants with NIHTB-CB, cognition-specific PROMs and standardized rating scales. The NIHTB-CB will be administered at baseline, 3 weeks (± 1 week), and at 1 year, to investigate the test-retest reliability and practice effects, an attribute that is critical for FDA’s approval for any PerfO measure. Innovation: This proposal is the first to investigate whether the NIHTB-CB holds promise as a PerfO measure of cognition in DMD. We bring a team science approach to improve the cognitive research footprint in DMD. The completion of our study will provide the scientific rationale to adopt the NIH Toolbox as a PerfO measure of cognition in clinical trials in DMD.