Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

Muscular Dystrophies Clinical Trial

— GRASP-01-001  

Official title:

GRASP-LGMD: Defining Clinical Endpoints in LGMD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03981289
• Other study ID #: HM20018721
• Secondary ID: GRASP-LGMD
• Status: Recruiting
• Start date: June 14, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: Virginia Commonwealth University
• Contact: Ruby Langeslay
• Phone: 804-828-8481
• Email: Ruby.Langeslay[@]vcuhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Limb Girdle Muscular Dystrophy
• Muscular Dystrophies

Locations

Country	Name	City	State
United Kingdom	Newcastle University	Newcastle
United Kingdom	John Walton Muscular Dystrophy Research Centre (Newcastle upon Tyne)	Newcastle Upon Tyne
United States	The University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	University of California Irvine	Irvine	California
United States	Kansas University Medical Center	Kansas City	Kansas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (10)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Hugo W. Moser Research Institute at Kennedy Krieger, Inc., Nationwide Children's Hospital, Newcastle University, University of California, Irvine, University of Colorado Anschutz Medical Center, University of Iowa, University of Kansas, University of Minnesota, Washington University School of Medicine

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mobility	Mobility will be measured using the 100 Meter Timed Test (100m) in which the participant is asked to complete 2 laps around 2 cones set 25 meters apart as quickly as safely possible, running if able, and the time in seconds is recorded.	Baseline to 12 months
Primary	Change in motor performance	The 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.	Baseline to 12 months
Primary	Change in upper limb function characteristics	The Performance of Upper Limb 2.0 (PUL) scale measures the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy. There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest.	Baseline to 12 months
Primary	Change in workspace volume	Workspace volume (WSV) will be measured using ACTIVE, an interactive video game which will calculate the combination of upper extremity and trunk strength and function in cubic meters.	Baseline to 12 months
Primary	Change in Forced vital capacity (FVC)	Volume of air forcefully exhaled will be measured using Spirometry performed in a sitting position using standardized equipment	Baseline to 12 months
Primary	Changes in Forced expiratory volume (FEV1)	Volume of air forcefully exhaled in one second will be measured using Spirometry performed in a sitting position using standardized equipment	Baseline to 12 months
Primary	Change in activity limitations	ACTIVLIM is a patient-reported measure of activity limitations for individuals with upper and/or lower limb impairments, which measures the ability to perform daily activities.	Baseline to 12 months
Primary	Change in upper extremity disability	The Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) questionnaire measures levels of disability in an individual's upper extremity.	Baseline to 12 months
Primary	Change in self-reported physical health	PROMIS Physical Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general physical health by assessing fatigue, pain intensity, pain interference, physical function, sleep disturbance, dyspnea, gastrointestinal symptoms, itch, pain behavior, pain quality, sexual function, and sleep related impairment.	Baseline to 12 months
Primary	Change in self-reported mental health	PROMIS Mental Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general mental health by assessing anxiety, depression, alcohol use, anger, cognitive function, life satisfaction, meaning and purpose, positive affect, psychosocial illness impact, self-efficacy for managing chronic conditions, smoking, and substance use	Baseline to 12 months
Primary	Change in self-reported social health	PROMIS Social Health is part of a set of patient-reported measures developed by a National Institute of Health that evaluates general social health by assessing ability to participate in social roles and activities, companionship, satisfaction with social roles and activities, social isolation, and social support.	Baseline to 12 months
Primary	Change in whole body health	The Quality of Life in Genetic Neuromuscular Disease Questionnaire was developed to measure whole-body health impact in neuromuscular diseases.	Baseline to 12 months
Primary	Change in overall health	Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.	Baseline to 12 months