Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study.
Clinical outcome assessments
Clinical trials
Limb girdle muscular dystrophy
Muscular dystrophy
Therapeutic development
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
15 Mar 2024
15 Mar 2024
Historique:
received:
19
09
2023
accepted:
26
02
2024
medline:
18
3
2024
pubmed:
16
3
2024
entrez:
16
3
2024
Statut:
epublish
Résumé
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. 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). 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. Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019.
Sections du résumé
BACKGROUND
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
METHODS
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
CONCLUSIONS
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
BACKGROUND
Clinicaltrials.gov NCT03981289; Date of registration: 6/10/2019.
Identifiants
pubmed: 38491364
doi: 10.1186/s12883-024-03588-1
pii: 10.1186/s12883-024-03588-1
doi:
Substances chimiques
DNAJB6 protein, human
0
Nerve Tissue Proteins
0
Molecular Chaperones
0
HSP40 Heat-Shock Proteins
0
FKRP protein, human
EC 2.4.2.-
Pentosyltransferases
EC 2.4.2.-
ANO5 protein, human
0
Anoctamins
0
Banques de données
ClinicalTrials.gov
['NCT03981289']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
96Subventions
Organisme : NCATS NIH HHS
ID : 1R21TR003184
Pays : United States
Investigateurs
Kathy Mathews
(K)
Doris Leung
(D)
Peter Kang
(P)
Urvi Desai
(U)
John Vissing
(J)
Carla Zingariello
(C)
Stacy Dixon
(S)
Informations de copyright
© 2024. The Author(s).
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