定义肢带型肌营养不良症的临床终点：GRASP-LGMD 研究。

Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study.

机构信息

Virginia Commonwealth University, Richmond, VA, USA.

Nationwide Children's Hospital, Columbus, OH, USA.

出版信息

BMC Neurol. 2024 Mar 15;24(1):96. doi: 10.1186/s12883-024-03588-1.

DOI:10.1186/s12883-024-03588-1

PMID:38491364

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10941356/

Abstract

BACKGROUND

The Limb Girdle Muscular Dystrophies (LGMDs) are characterized by progressive weakness of the shoulder and hip girdle muscles as a result of over 30 different genetic mutations. This study is designed to develop clinical outcome assessments across the group of disorders.

METHODS/DESIGN: The primary goal of this study is to evaluate the utility of a set of outcome measures on a wide range of LGMD phenotypes and ability levels to determine if it would be possible to use similar outcomes between individuals with different phenotypes. We will perform a multi-center, 12-month study of 188 LGMD patients within the established Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Research Consortium, which is comprised of 11 sites in the United States and 2 sites in Europe. Enrolled patients will be clinically affected and have mutations in CAPN3 (LGMDR1), ANO5 (LGMDR12), DYSF (LGMDR2), DNAJB6 (LGMDD1), SGCA (LGMDR3), SGCB (LGMDR4), SGCD (LGMDR6), or SGCG (LGMDR5, or FKRP-related (LGMDR9).

DISCUSSION

To the best of our knowledge, this will be the largest consortium organized to prospectively validate clinical outcome assessments (COAs) in LGMD at its completion. These assessments will help clinical trial readiness by identifying reliable, valid, and responsive outcome measures as well as providing data driven clinical trial decision making for future clinical trials on therapeutic agents for LGMD. The results of this study will permit more efficient clinical trial design. All relevant data will be made available for investigators or companies involved in LGMD therapeutic development upon conclusion of this study as applicable.

TRIAL REGISTRATION

Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019.

摘要

背景

肢带型肌营养不良症（LGMDs）的特征是由于 30 多种不同的基因突变导致肩部和臀部带肌进行性无力。本研究旨在针对该组疾病制定临床结局评估。

方法/设计：本研究的主要目的是评估一组广泛 LGMD 表型和能力水平的结局测量的效用，以确定是否可以在不同表型的个体之间使用类似的结局。我们将在美国的 11 个地点和欧洲的 2 个地点的既定遗传分辨率和评估解决 LGMD 表型（GRASP-LGMD）研究联盟内进行一项为期 12 个月的 188 例 LGMD 患者的多中心研究。入组患者将具有临床症状并携带 CAPN3（LGMDR1）、ANO5（LGMDR12）、DYSF（LGMDR2）、DNAJB6（LGMDD1）、SGCA（LGMDR3）、SGCB（LGMDR4）、SGCD（LGMDR6）或 SGCG（LGMDR5）突变，或 FKRP 相关（LGMDR9）。

讨论

据我们所知，这将是最大的联盟，旨在在完成时前瞻性验证 LGMD 的临床结局评估（COA）。这些评估将通过识别可靠、有效和敏感的结局测量来帮助临床试验准备，并为未来治疗 LGMD 的治疗剂临床试验提供数据驱动的临床试验决策。这项研究的结果将允许更有效的临床试验设计。所有相关数据将在本研究结束后可供参与 LGMD 治疗开发的研究人员或公司使用。