Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

Brief Title

Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

Official Title

GRASP LGMD Defining Clinical Endpoints in LGMD

Brief Summary

      Limb Girdle Muscular Dystrophy comprise a group of disorders made up of over 30 mutations
      which share a common phenotype of progressive weakness of the shoulder and hip girdle
      muscles. While the individual genetic mutations are rare, as a cohort, LGMDs are one of the
      four most common muscular dystrophies. The overall goal of project 1 is to define the key
      phenotypes as measured by standard clinical outcome assessments (COAs) for limb girdle
      muscular dystrophies (LGMD) to hasten therapeutic development.
    

Detailed Description

      The genetic heterogeneity has been a barrier to broad natural history efforts, with prior
      investigations often limited to single gene mutations. Much attention is paid to the
      variability within individual mutations (e.g. distal presentations), as opposed to defining
      the best strategy for measuring change in overall LGMD disease burden. This presents a major
      dilemma for LGMD rare disease research: how to balance diverse genes leading to overlapping
      phenotypes, versus variants in the same gene leading to divergent phenotypes. What is clear,
      is as a group, LGMDs are chronic and progressive leading to significant lifetime morbidity
      and represent a large unmet clinical need.

      Recent developments in the investigator's genetic understanding of LGMD and molecular
      approaches to therapy have led to proposed gene replacement therapies for at least three of
      the LGMD mutations. Several of these gene replacement therapies are currently in
      pre-clinical/phase 1 testing, leading to an urgent need for natural history data. In
      addition, non-specific therapies which target muscle mass or function are being tested in
      other muscular dystrophies and may prove beneficial for LGMD.
    


Study Type

Observational


Primary Outcome

Change in mobility


Condition

Limb Girdle Muscular Dystrophy


Study Arms / Comparison Groups

 CAPN3 (LGMD2A)
Description:  Clinical Assessments, Biomarkers

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

80

Start Date

June 14, 2019

Completion Date

December 2022

Primary Completion Date

August 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Age between 4-65 at enrollment

          -  Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle
             pattern, or in a distal extremity)

          -  A genetically or functionally confirmed mutation in ANO5, CAPN3, DYSF, DNAJB6 or
             SGCA-G.

          -  Ambulatory

        Exclusion Criteria:

          -  Non-ambulatory at the time of enrollment.

          -  Any other illness that would interfere with the ability to undergo safe testing or
             would interfere with interpretation of the results in the opinion of the site
             investigator.
      

Gender

All

Ages

4 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Nicholas Johnson, MD, 807-828-7887, [email protected]

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT03981289

Organization ID

HM20015565

Secondary IDs

HM20018721

Responsible Party

Sponsor

Study Sponsor

Virginia Commonwealth University

Collaborators

 Newcastle University

Study Sponsor

Nicholas Johnson, MD, Principal Investigator, Virginia Commonwealth University


Verification Date

September 2021