Clinical trial NCT03981289: Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)
Official title: GRASP-LGMD: Defining Clinical Endpoints in LGMD
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Limb Girdle Muscular Dystrophy
Muscular Dystrophies
Keywords: LGMD
Limb Girdle Muscular Dystrophy
CAPN3
ANO5
DYSF
DNAJB6
Sarcoglycan
SGCA
SGCB
SGCD
SGCG
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: Newcastle University
name: Nationwide Children's Hospital
name: Washington University School of Medicine
name: University of Iowa
name: University of Minnesota
name: University of California, Irvine
name: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
name: University of Colorado, Denver
name: University of Kansas Medical Center
First posted: 2019-06-10
Enrollment: 80
Sex: ALL
Minimum age (years): 4
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: GRASP-LGMD covers a broad geographical distribution and we expect the race and ethnicity to match that of the United States. However, past experience in both the clinical and research LGMD populations shows that some minority subgroups are under-represented in research studies. To assist with recruitment of persons from diverse backgrounds we will utilize the Community and Special Populations Engagement Personnel supported through the CTSA networks to reach out to under-represented communities through a variety of local techniques which could include direct outreach, advertising with local advocacy groups, organizations, or newsletters, and local advertising using a variety of media which could include Social Media (e.g. Facebook, Twitter), radio, and newspapers.

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.

Eligibility criteria: Inclusion Criteria - Arm 1:

* 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.
* Willing and able to give informed consent and follow all study procedures and requirements

Inclusion Criteria - Arm 2:

* 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 confirmed mutation in SGCA-G
* Willing and able to give informed consent and follow all study procedures and requirements

Exclusion Criteria - Arm 1:

* 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.
* History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant.
* Positive pregnancy test at time any timepoint during the trial.

Exclusion Criteria - Arm 2:

* 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.
* History of a bleeding disorder, platelet count \<50,000, current use of an anticoagulant
* Positive pregnancy test at time any timepoint during the trial.

Primary outcomes:
measure: Change in mobility
timeFrame: Baseline to 12 months
measure: Change in motor performance
timeFrame: Baseline to 12 months
measure: Change in upper limb function characteristics
timeFrame: Baseline to 12 months
measure: Change in workspace volume
timeFrame: Baseline to 12 months
measure: Change in Forced vital capacity (FVC)
timeFrame: Baseline to 12 months
measure: Changes in Forced expiratory volume (FEV1)
timeFrame: Baseline to 12 months
measure: Change in activity limitations
timeFrame: Baseline to 12 months
measure: Change in upper extremity disability
timeFrame: Baseline to 12 months
measure: Change in self-reported physical health
timeFrame: Baseline to 12 months
measure: Change in self-reported mental health
timeFrame: Baseline to 12 months
measure: Change in self-reported social health
timeFrame: Baseline to 12 months
measure: Change in whole body health
timeFrame: Baseline to 12 months
measure: Change in overall health
timeFrame: Baseline to 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Aurora
country: United States
facility: The University of Colorado Anschutz Medical Campus
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Newcastle
country: United Kingdom
facility: John Walton Muscular Dystrophy Research Centre (Newcastle Upon Tyne)
Study officials:
affiliation: Virginia Commonwealth University
name: Nicholas Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: