Limb Girdle Muscular DystrophyGRASP-01-001NCT03981289
Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)
An observational study of Limb Girdle Muscular Dystrophy and Muscular Dystrophies, run by Virginia Commonwealth University at 10 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 4 to 65 years
- Conditions the study is for
- Limb Girdle Muscular Dystrophy, Muscular Dystrophies
- How many people
- 116 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 14 Jun 2019to 30 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: GRASP-LGMD covers a broad geographical distribution and we expect the race and ethnicity to match that of the United States. However, past experience in both the clinical and research LGMD populations shows that some minority subgroups are under-represented in research studies. To assist with recruitment of persons from diverse backgrounds we will utilize the Community and Special Populations Engagement Personnel supported through the CTSA networks to reach out to under-represented communities through a variety of local techniques which could include direct outreach, advertising with local advocacy groups, organizations, or newsletters, and local advertising using a variety of media which could include Social Media (e.g. Facebook, Twitter), radio, and newspapers.
Who may be able to join
- 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
- 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
Who cannot join
- 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.
- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
The University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Iowa
Iowa City, Iowa, 52242
University of California Irvine
Irvine, California, 92697
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of Minnesota
Minneapolis, Minnesota, 55455
Virginia Commonwealth University
Richmond, Virginia, 23298
Washington University School of Medicine
St Louis, Missouri, 63110
United Kingdom1 site
John Walton Muscular Dystrophy Research Centre (Newcastle Upon Tyne)
Newcastle
About this study
Official title: GRASP-LGMD: Defining Clinical Endpoints in LGMD
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.
Read the 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.
- Keywords
- LGMD, Limb Girdle Muscular Dystrophy, CAPN3, ANO5, DYSF, DNAJB6, Sarcoglycan, SGCA, SGCB, SGCD, SGCG
- Medical subject headings
- Muscular Dystrophies, Limb-Girdle, Muscular Dystrophies, Muscular Dystrophy, Limb-Girdle, Type 1D
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
Change in Forced vital capacity (FVC)
Volume of air forcefully exhaled will be measured using Spirometry performed in a sitting position using standardized equipment
Measured: Baseline to 12 months
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
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
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.
Measured: Baseline to 12 months
Change in overall health
Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start14 Jun 2019
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Limb Girdle Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University, Nationwide Children's Hospital, Washington University School of Medicine, University of Iowa, University of Minnesota, University of California, Irvine, Hugo W. Moser Research Institute at Kennedy Krieger, Inc., University of Colorado, Denver, University of Kansas Medical Center
- Responsible party
- Sponsor
- Investigators
- Nicholas Johnson, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03981289
- Sponsor's protocol ID
- HM20018721
- Other IDs
- GRASP-LGMD
- Acronym
- GRASP-01-001
- Status last verified
- Feb 2026
- First submitted
- 3 Jun 2019
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the LGMD investigators
Publications
Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews KD, Weihl CC, Wicklund M, Hung M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study. BMC Neurol. 2024 Mar 15;24(1):96. doi: 10.1186/s12883-024-03588-1.
PubMed 38491364Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews K, Weihl CC, Wicklund M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study. Res Sq [Preprint]. 2023 Oct 6:rs.3.rs-3370395. doi: 10.21203/rs.3.rs-3370395/v1.
PubMed 37886601
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRASP-LGMD: Defining Clinical Endpoints in LGMD
- ClinicalTrials.gov ID
- NCT03981289
- Acronym / sponsor ID
- GRASP-01-001 / HM20018721
- Keywords
- LGMD, Limb Girdle Muscular Dystrophy, CAPN3, ANO5, DYSF, DNAJB6, Sarcoglycan, SGCA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Newcastle University, Nationwide Children's Hospital, Washington University School of Medicine, University of Iowa, University of Minnesota, University of California, Irvine, Hugo W. Moser Research Institute at Kennedy Krieger, Inc., University of Colorado, Denver, University of Kansas Medical Center
- Study start
- 14 Jun 2019 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 10 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 4 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- GRASP-LGMD covers a broad geographical distribution and we expect the race and ethnicity to match that of the United States. However, past experience in both the clinical and research LGMD populations shows that some minority subgroups are under-represented in research studies. To assist with recruitment of persons from diverse backgrounds we will utilize the Community and Special Populations Engagement Personnel supported through the CTSA networks to reach out to under-represented communities through a variety of local techniques which could include direct outreach, advertising with local advocacy groups, organizations, or newsletters, and local advertising using a variety of media which could include Social Media (e.g. Facebook, Twitter), radio, and newspapers.
Key inclusion criteria (8 listed)
- 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
- Age between 4-65 at enrollment
Key exclusion criteria (6 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in mobility
Time frame: 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
Time frame: 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
Time frame: 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 Forced vital capacity (FVC)
Time frame: 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)
Time frame: 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
Time frame: 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 self-reported physical health
Time frame: 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 overall health
Time frame: Baseline to 12 months
Domain Delta Questionnaire is a patient reported measure that assesses overall health over the previous 12 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2026.
- Derived from this study: PubMed 38491364Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews KD, Weihl CC, Wicklund M, Hung M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining clinical endpoints in limb girdle muscular dystrophy: a GRASP-LGMD study. BMC Neurol. 2024 Mar 15;24(1):96. doi: 10.1186/s12883-024-03588-1.
- Derived from this study: PubMed 37886601Doody A, Alfano L, Diaz-Manera J, Lowes L, Mozaffar T, Mathews K, Weihl CC, Wicklund M, Statland J, Johnson NE; GRASP-LGMD Consortium. Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy: A GRASP-LGMD study. Res Sq [Preprint]. 2023 Oct 6:rs.3.rs-3370395. doi: 10.21203/rs.3.rs-3370395/v1.
- Individual participant dataSharing planned: No. Aggregated and deidentified data will be shared with qualified investigators upon majority approval of the LGMD investigators
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas Johnson, MD principal investigator
Virginia Commonwealth University
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Limb Girdle Muscular Dystrophy and Muscular Dystrophies, run by Virginia Commonwealth University at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mobility (time frame: Baseline to 12 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03981289, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.