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Completed

NCT Number: NCT04202627

Biomarker Development in LGMD2i

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.

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Key information

Conditions

Muscular Dystrophies Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Limb Girdle Muscular Dystrophy Muscular Diseases Muscular Disorders, Atrophic Muscular Dystrophies, Limb-Girdle Muscular Dystrophy, Limb-Girdle, Type 2I Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases

Age range

10 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Copenhagen Neuromuscular Center, Copenhagen, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  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 outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

ML Bio Solutions, Inc.

Industry

Collaborators

  • Virginia Commonwealth University

Registry information

Acronym: MLB-01-001

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Dec 17, 2019
Registry last updated
Mar 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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