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

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

Amy Doody  1 , Lindsay Alfano  2 , Jordi Diaz-Manera  3 , Linda Lowes  2 , Tahseen Mozaffar  4 , Katherine D Mathews  5 , Conrad C Weihl  6 , Matthew Wicklund  7 , Man Hung  8 , Jeffrey Statland  9 , Nicholas E Johnson  10 ; GRASP-LGMD Consortium
Collaborators, Affiliations

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

Amy Doody et al. BMC Neurol. .

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.

Keywords: Clinical outcome assessments; Clinical trials; Limb girdle muscular dystrophy; Muscular dystrophy; Therapeutic development.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
GRASP-LGMD Consortium participating institutions. Adapted from Wikimedia Commons [40, 41]
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