Clinical trial NCT04202627: Biomarker Development in LGMD2i
Official title: Biomarker Development in LGMD2i
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Muscular Dystrophies
Limb Girdle Muscular Dystrophy
Keywords: LGMD
FKRP
Clinical Research
ML Bio Solutions
Limb Girdle Muscular Dystrophy
Limb girdle muscular dystrophy type R9 (LGMD R9)
LGMD2i
Lead sponsor: ML Bio Solutions, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Virginia Commonwealth University
First posted: 2019-12-17
Enrollment: 101
Sex: ALL
Minimum age (years): 10
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Study participants will be identified through self-selection and direct recruitment options. Participants will be identified from the population of individuals who are followed at the neuromuscular clinics. Participants will also be solicited from the Global FKRP registry.

Brief summary: The overall goal of this natural history study is to define the key LGMD2i phenotypes as measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker for LGMD2i to support therapeutic development.

Detailed description: Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due to missense mutations in the Fukutin-related protein (FKRP) gene. Patients develop progressive proximal muscle weakness that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and respiratory compromise.

There are promising new therapies that have been developed and as a result therapeutic trials are approaching.

The rationale for this study is to define appropriate COAs for LGMD2i, which will facilitate therapeutic development and ensure properly powered clinical trials. In addition, measurement of dystroglycan in muscles represents a potential muscle biomarker that could be used in early phase clinical trials as a measure of target engagement. The clinical utility of changes in dystroglycan has not been validated in human samples.

Eligibility criteria: Inclusion Criteria:

* Age between 10-65 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 FKRP (LGMD2i)
* Willing and able to give informed consent and follow all procedures and requirements

Exclusion Criteria:

* 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
* A 10-meter walk time of \<4 seconds

Primary outcomes:
measure: 10-Meter walk (10 MWT) -mobility
timeFrame: Through study completion at 12 months
measure: 100-Meter Timed Test (100m) - mobility
timeFrame: Through study completion at 12 months
measure: NSAD- Motor performance
timeFrame: Through study completion at 12 months
measure: Timed up-and-go (TUG) - mobility
timeFrame: Through study completion at 12 months
measure: FVC - Pulmonary function
timeFrame: Through study completion at 12 months
measure: Timed 4 stair Climb (4SC) - mobility
timeFrame: Through study completion at 12 months
measure: 9 Hole Peg Test (9HPT) - distal upper extremity function
timeFrame: Through study completion at 12 months
measure: Performance of Upper Limb (PUL 2.0) - limb function
timeFrame: Through study completion at 12 months
measure: Hand Held Dynamometry (HHD) - isometric strength
timeFrame: Through study completion at 12 months
Secondary outcomes:
measure: To develop clinical outcome assessments for LGMD2i
timeFrame: Through study completion at 12 months
Other outcomes:
measure: To validate potential biomarkers
timeFrame: Baseline, Month 6
measure: To understand the change from baseline in muscle mass using Magnetic Resonance Imaging
timeFrame: Baseline, Month 6, Month 12
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
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: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Copenhagen
country: Denmark
facility: Copenhagen Neuromuscular Center
Study officials:
affiliation: Virginia Commonwealth University
name: Nicholas E Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: