GRASP: Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)

Sponsor

Virginia Commonwealth University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03981289

Collaborator

Newcastle University (Other), University of California, Irvine (Other), University of Kansas (Other), University of Colorado, Denver (Other), Nationwide Children's Hospital (Other), Washington University School of Medicine (Other), University of Iowa (Other), Hugo W. Moser Research Institute at Kennedy Krieger, Inc. (Other), University of Florida (Other), Brigham and Women's Hospital (Other)

Enrollment

Locations

41.6

Anticipated Duration (Months)

7.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Limb Girdle Muscular Dystrophy Muscular Dystrophies

Detailed 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

GRASP LGMD Defining Clinical Endpoints in LGMD

Actual Study Start Date :

Jun 14, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
CAPN3 (LGMD2A) Clinical Assessments, Biomarkers
DYSF (LGMD2B) Clinical Assessments, Biomarkers
ANO5 (LGMD2L) Clinical Assessments, Biomarkers
DNAJB6 (LGMD1D) Clinical Assessments, Biomarkers
Sarcoglycan (LGMD2D) (LGMD2E) (LGMD2C) (LGMD2F) Clinical assessments

Outcome Measures

Primary Outcome Measures

Change in mobility [Baseline to 12 months]
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.
Change in motor performance [Baseline to 12 months]
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.
Change in upper limb function characteristics [Baseline to 12 months]
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.
Change in workspace volume [Baseline to 12 months]
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.
Change in Forced vital capacity (FVC) [Baseline to 12 months]
Volume of air forcefully exhaled will be measured using Spirometry performed in a sitting position using standardized equipment
Changes in Forced expiratory volume (FEV1) [Baseline to 12 months]
Volume of air forcefully exhaled in one second will be measured using Spirometry performed in a sitting position using standardized equipment
Change in activity limitations [Baseline to 12 months]
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.
Change in upper extremity disability [Baseline to 12 months]
The Disabilities of the Arm, Shoulder, and Hand Questionnaire (DASH) questionnaire measures levels of disability in an individual's upper extremity.
Change in self-reported physical health [Baseline to 12 months]
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.
Change in self-reported mental health [Baseline to 12 months]
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
Change in self-reported social health [Baseline to 12 months]
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.
Change in whole body health [Baseline to 12 months]
The Quality of Life in Genetic Neuromuscular Disease Questionnaire was developed to measure whole-body health impact in neuromuscular diseases.
Change in overall health [Baseline to 12 months]
Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Ambulatory

Exclusion Criteria:

Non-ambulatory at the time of enrollment.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California Irvine	Irvine	California	United States	92697
2	UC Denver	Aurora	Colorado	United States	80045
3	University of Florida	Gainesville	Florida	United States	32608
4	University of Iowa	Iowa City	Iowa	United States	52242
5	Kansas University Medical Center	Kansas City	Kansas	United States	66160
6	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
7	Brigham and Women's	Boston	Massachusetts	United States	02115
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
10	Virginia Commonwealth University	Richmond	Virginia	United States	23298
11	Newcastle University	Newcastle		United Kingdom