Biomarker Development in LGMD2i

NCT04202627 | Completed DMC

• 1 other identifier: HM20018755
• Study Type: observational
• Target: 101
• Locations: 2 countries
• Sites: 11

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.

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

Outcome Measures

Primary Outcomes (9)

• 10-Meter walk (10 MWT) -mobility

  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

  Through study completion at 12 months

• 100-Meter Timed Test (100m) - mobility

  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.

  Through study completion at 12 months

• NSAD- Motor performance

  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.

  Through study completion at 12 months

• Timed up-and-go (TUG) - mobility

  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.

  Through study completion at 12 months

• FVC - Pulmonary function

  The total amount of air exhaled during the forced expiratory volume test (Forced vital capacity - FVC) will be assessed in a sitting position only.

  Through study completion at 12 months

• Timed 4 stair Climb (4SC) - mobility

  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.

  Through study completion at 12 months

• 9 Hole Peg Test (9HPT) - distal upper extremity function

  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.

  Through study completion at 12 months

• Performance of Upper Limb (PUL 2.0) - limb function

  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.

  Through study completion at 12 months

• Hand Held Dynamometry (HHD) - isometric strength

  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.

  Through study completion at 12 months

Secondary Outcomes (1)

• To develop clinical outcome assessments for LGMD2i

  Through study completion at 12 months

Other Outcomes (2)

• To validate potential biomarkers

  Baseline, Month 6

• To understand the change from baseline in muscle mass using Magnetic Resonance Imaging

  Baseline, Month 6, Month 12

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ML Bio Solutions, Inc.: lead
• Virginia Commonwealth University: collaborator

Study Sites (11)

University of California Irvine

Irvine, California, 92697, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Atrium Health

Charlotte, North Carolina, 28207, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Copenhagen Neuromuscular Center

Copenhagen, Denmark

Location

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.

MeSH Terms

Conditions

Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Limb-Girdle, Type 2I

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Nicholas E Johnson, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2019
• First Posted: December 17, 2019
• Study Start: December 1, 2019
• Primary Completion: October 10, 2022
• Study Completion: October 10, 2022
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); US (10)