PAR-18-953 (ASCOT-DMD)

项目摘要 这种应用的前提是肌营养不良症的战略优先事项 国家卫生研究院(NIH)协调委员会(MDCC)和我们的临床 Duchenne肌营养不良症(DMD)的认知研究经验。认知健康 是影响DMD患者生活质量的关键因素之一。预期寿命的提高， 伴随着这个罕见疾病领域令人兴奋的药物开发和药物批准的步伐 为更全面地治疗DMD的认知症状提供了一个背景。这个 临床前的成功可以通过建立敏感的和 稳健的绩效-结果(Perfo)认知测量。在这个应用程序中，我们带来了一个团队 科学方法，利用Thangarajh、Adams和Kaat to博士的研究专长 调查NIH工具箱认知电池(NIHTB-CB)的强度，作为一种性能- DMD认知功能的结果测量。NIHTB-CB允许测量的连续性，满足 美国国立卫生研究院要求科学严谨和重复性，并可扩展用于多点临床试验， 不同于黄金标准的神经心理测试不能高保真地应用于临床 试验设置。该提案的具体目标是建立(I)重测信度和 NIHTB-CB的实践效果，(Ii)使用患者报告的结果测量(PROMS)来 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。这项前瞻性的纵向研究将评估 46名参与者使用NIHTB-CB、认知特异型PROMS和标准化评定量表。这个 NIHTB-CB将在基线、3周(±1周)和1年时应用，以调查 重测可靠性和实践效果，这一属性对于FDA批准任何 Perfo度量。创新：这项提案是第一个调查NIHTB-CB是否成立的提案 承诺作为DMD认知功能的一项绩效测量。我们带来了团队科学的方法来改进 认知研究在DMD中的足迹。我们的研究的完成将为我们提供科学的 在DMD的临床试验中采用NIH工具箱作为认知的最佳测量的理由。

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.