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Biomarker Development in LGMD2i (MLB-01-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04202627
Recruitment Status : Completed
First Posted : December 17, 2019
Last Update Posted : March 29, 2023
Virginia Commonwealth University
Information provided by (Responsible Party):
ML Bio Solutions, Inc.

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.

Condition or disease
Muscular Dystrophies Limb Girdle Muscular Dystrophy

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.

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Study Type : Observational
Actual Enrollment : 101 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Biomarker Development in LGMD2i
Actual Study Start Date : December 1, 2019
Actual Primary Completion Date : October 10, 2022
Actual Study Completion Date : October 10, 2022

Primary Outcome Measures :
  1. 10-Meter walk (10 MWT) -mobility [ Time Frame: Through study completion at 12 months ]

    The 10 MWT will be used to determine the ambulatory Cohort for of all subjects. For the purposes of this study, the definitions for ambulation are as follows:

    • Cohort A: completes the 10 MWT unaided in ≥ 4 to ≤ 12 seconds
    • Cohort B: completes the walk unaided in > 12 seconds or is non-ambulatory

  2. 100-Meter Timed Test (100m) - mobility [ Time Frame: Through study completion at 12 months ]
    The 100m timed test is designed to capture maximal ambulatory capacity. The participant will be asked to complete 4 full laps around 2 cones set 25 meters apart as quickly and as safely as possible, including running if able. This will not be assessed in participants with a 10-meter walk time greater than 12 seconds.

  3. NSAD- Motor performance [ Time Frame: Through study completion at 12 months ]
    North Star Assessment for Dysferlinopathy (NSAD) is a functional scale specifically designed to measure motor performance in individuals with LGMD. It consists of 29 items that are considered clinically relevant items from the North Star Ambulatory Assessment and the Motor Function Measure 20 with a maximum score of 54 and higher scores indicate higher functional abilities.

  4. Timed up-and-go (TUG) - mobility [ Time Frame: Through study completion at 12 months ]
    The TUG is an assessment used to evaluate functional ambulation, balance, and fall risk. The fastest time to rise from a chair, walk 3 meters, and return to sitting independently without an assistive device will be recorded. This will not be assessed in Cohort B participants.

  5. FVC - Pulmonary function [ Time Frame: Through study completion at 12 months ]
    The total amount of air exhaled during the forced expiratory volume test (Forced vital capacity - FVC) will be assessed in a sitting position only.

  6. Timed 4 stair Climb (4SC) - mobility [ Time Frame: Through study completion at 12 months ]
    The 4SC quantifies the time required for the participant to ascend 4 standard steps. This will not be assessed in participants with a 10 meter walk time greater than 12 seconds.

  7. 9 Hole Peg Test (9HPT) - distal upper extremity function [ Time Frame: Through study completion at 12 months ]
    The 9HPT is a quantitative measure of distal upper extremity function. It measures the time required for patients to place 9 pegs in the 9 holes on the board and then remove them as quickly as possible.

  8. Performance of Upper Limb (PUL 2.0) - limb function [ Time Frame: Through study completion at 12 months ]
    The PUL is a tool designed for assessing upper limb function in persons with neuromuscular disorders. It was developed as a conceptual framework reflecting the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy (DMD). There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest.

  9. Hand Held Dynamometry (HHD) - isometric strength [ Time Frame: Through study completion at 12 months ]
    HHD using the MicroFET2 myometer will be utilized to capture isometric strength in target muscle groups. Maximum strength in kilograms will be reported for each muscle group provided a continuous scale variable for analysis.

Secondary Outcome Measures :
  1. To develop clinical outcome assessments for LGMD2i [ Time Frame: Through study completion at 12 months ]
    To determine the sensitivity of the COAs to longitudinal disease progression

Other Outcome Measures:
  1. To validate potential biomarkers [ Time Frame: Baseline, Month 6 ]

    To develop a reliable measure of dystroglycosylation in human skeletal muscle by using fresh tissue biopsy.

    A muscle biopsy will be collected at baseline and 6 months from the right tibialis anterior. The biopsy site will be uniform between investigators. The investigators will utilize a 14-gauge Supercore biopsy instrument to take a total of three aspirations from the same site.

  2. To understand the change from baseline in muscle mass using Magnetic Resonance Imaging [ Time Frame: Baseline, Month 6, Month 12 ]
    To understand the change from baseline in muscle mass using Magnetic Resonance Imaging

Biospecimen Retention:   Samples With DNA
Blood and Tissue samples will be taken for biomarker development and retained for future research. No clinical diagnosis will be given to patients.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   10 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04202627

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United States, California
University of California Irvine
Irvine, California, United States, 92697
United States, Colorado
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States, 80045
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Atrium Health
Charlotte, North Carolina, United States, 28207
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Copenhagen Neuromuscular Center
Copenhagen, Denmark
Sponsors and Collaborators
ML Bio Solutions, Inc.
Virginia Commonwealth University
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Principal Investigator: Nicholas E Johnson, MD Virginia Commonwealth University
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Responsible Party: ML Bio Solutions, Inc.
ClinicalTrials.gov Identifier: NCT04202627    
Other Study ID Numbers: HM20018755
First Posted: December 17, 2019    Key Record Dates
Last Update Posted: March 29, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ML Bio Solutions, Inc.:
Clinical Research
ML Bio Solutions
Limb Girdle Muscular Dystrophy
Limb girdle muscular dystrophy type R9 (LGMD R9)
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophies, Limb-Girdle
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn