Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A.
Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A.
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DOI：
10.3389/fneur.2022.930435
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发表时间：
2022
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
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作者：
随着Charcot-Marie-Tooth 1A型（CMT 1A）治疗试验的开展，可靠，有效和反应性的临床结局评估和生物标志物至关重要。加速CMT临床试验（ACT-CMT）是一项国际研究，旨在解决CMT 1A临床试验准备就绪方面的重要差距，包括缺乏针对成人的经验证的反应性功能结局指标，以及缺乏经验证的生物标志物用于CMT 1A临床试验的多中心应用。ACT-CMT的主要目的包括验证Charcot-Marie-Tooth功能结局指标、肌内脂肪蓄积作为下肢运动生物标志物的磁共振成像以及触觉小体感觉受体密度（感觉生物标志物）的体内反射共聚焦显微镜检查。初步研究表明，这些措施是可行、可靠和有效的。一项大型的前瞻性、多中心研究是必要的，以充分验证和检查这些结局指标与现有结局的反应性，以便在未来涉及CMT 1A个体的临床试验中使用。招募了215名CMT 1A成人参与这项前瞻性、国际性、多中心研究。进行长达3年的系列评估，包括CMT-FOM、CMT检查评分-Rasch、总体神经病变限制量表、CMT-健康指数以及神经传导研究、磁共振成像和迈斯纳小体生物标志物。将检查使用基线数据的相关性的有效性。纵向分析将记录功能、肌内脂肪积累、触觉小体感觉受体密度的变化。最后，我们将使用基于锚点的统计方法和其他统计方法来确定CMT 1A中这些临床结局评估和生物标志物的最小临床重要变化。在CMT 1A的早期和晚期临床试验中，迫切需要对功能和疾病进展生物标志物进行可靠且反应灵敏的临床结局评估。ACT-CMT研究方案将通过对新型和现有临床结局评估以及运动和感觉生物标志物进行前所未有的详细前瞻性、纵向、多中心检查来满足这一需求，并加强国际临床试验基础设施、培训和准备，以便为CMT和相关神经病的未来治疗试验做好准备。
With therapeutic trials on the horizon for Charcot-Marie-Tooth type 1A (CMT1A), reliable, valid, and responsive clinical outcome assessments and biomarkers are essential. Accelerate Clinical Trials in CMT (ACT-CMT) is an international study designed to address important gaps in CMT1A clinical trial readiness including the lack of a validated, responsive functional outcome measure for adults, and a lack of validated biomarkers for multicenter application in clinical trials in CMT1A. The primary aims of ACT-CMT include validation of the Charcot-Marie-Tooth Functional Outcome Measure, magnetic resonance imaging of intramuscular fat accumulation as a lower limb motor biomarker, and in-vivo reflectance confocal microscopy of Meissner corpuscle sensory receptor density, a sensory biomarker. Initial studies have indicated that these measures are feasible, reliable and valid. A large prospective, multi-site study is necessary to fully validate and examine the responsiveness of these outcome measures in relation to existing outcomes for use in future clinical trials involving individuals with CMT1A. Two hundred 15 adults with CMT1A are being recruited to participate in this prospective, international, multi-center study. Serial assessments, up to 3 years, are performed and include the CMT-FOM, CMT Exam Score-Rasch, Overall Neuropathy Limitations Scale, CMT-Health Index, as well as nerve conduction studies, and magnetic resonance imaging and Meissner corpuscle biomarkers. Correlations using baseline data will be examined for validity. Longitudinal analyses will document the changes in function, intramuscular fat accumulation, Meissner corpuscle sensory receptor density. Lastly, we will use anchor-based and other statistical methods to determine the minimally clinically important change for these clinical outcome assessments and biomarkers in CMT1A. Reliable, and responsive clinical outcome assessments of function and disease progression biomarkers are urgently needed for application in early and late phase clinical trials in CMT1A. The ACT-CMT study protocol will address this need through the prospective, longitudinal, multicenter examination in unprecedented detail of novel and existing clinical outcome assessments and motor and sensory biomarkers, and enhance international clinical trial infrastructure, training and preparedness for future therapeutic trials in CMT and related neuropathies.
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DOI：
10.1111/j.1529-8027.2011.00350.x
发表时间：
2011-09
期刊：
Journal of the peripheral nervous system : JPNS
影响因子：
--
作者：
Murphy SM;Herrmann DN;McDermott MP;Scherer SS;Shy ME;Reilly MM;Pareyson D
通讯作者：
Pareyson D
患者鉴定1A型charcot-marie-tooth病的症状影响。
影响因子：
--
作者：
Johnson NE;Heatwole CR;Ferguson M;Sowden JE;Jeanat S;Herrmann DN
通讯作者：
Herrmann DN
影响因子：
2.8
作者：
Johnson, Nicholas E.;Heatwole, Chad R.;Dilek, Nuran;Sowden, Janet;Kirk, Callyn A.;Shereff, Denise;Shy, Michael E.;Herrmann, David N.
通讯作者：
Herrmann, David N.
DOI：
10.1126/science.aaa4484
发表时间：
2015-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Das I;Krzyzosiak A;Schneider K;Wrabetz L;D'Antonio M;Barry N;Sigurdardottir A;Bertolotti A
通讯作者：
Bertolotti A
影响因子：
3.4
作者：
Fridman, Vera;Oaklander, Anne Louise;Eichler, Florian S.
通讯作者：
Eichler, Florian S.