Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD)
Study Details
Study Description
Brief Summary
The primary goal of this proposal is to collect motor and functional outcomes specific to FSHD over time. By collecting measures specific to FSHD, this will help ensure the best level of clinical care is being provided. Also, the hope is to speed up drug development by gaining a better understanding of how having FSHD impacts motor function and other health outcomes (i.e. breathing, wheelchair use, etc.) and how big a change in motor function would be clinically meaningful to those with FSHD.
Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) will have approximately 450 FSHD participants followed for a minimum of 3 years. A subset of MOVE FSHD participants, approximately 200, will participate in the MOVE+ sub-study which includes whole body MRI and muscle biopsy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| MOVE FSHD Study Visits Patients will receive standard of care as determined by their treating physician. Study visits will occur per standard of care and are anticipated to occur at least once a year. |
Outcome Measures
Primary Outcome Measures
- 10m walk/run [Baseline - 3 years]
The 10-meter walk/run (previously the 30 foot go) or gait speed task will be performed during study visits. This task tests a range of different abilities, from power, to endurance, and balance. Also, the 10 meter walk/run is a predictor of loss of ambulation in Duchenne Muscular Dystrophy.
- Shoulder and Arm Range of Motion [Baseline - 3 years]
Range of motion tasks mimicking lifting or reaching up will be performed.
- Shoulder and Arm Function [Baseline - 3 years]
Participants will be timed on stacking cans.
- Spirometry (FVC, FEV1, PCF) [Baseline - 3 years]
Investigators will obtain forced vital capacity and forced expiratory volume in 1 second, both standardized outcomes used commonly in clinic and clinical trials. Also, for sites who routinely collect Peak Cough Flow this will also be obtained.
Secondary Outcome Measures
- Trunk Function [Baseline - 3 years]
There are no specific functional tasks designed to measure trunk function in FSHD so Investigators have chosen a practical task that will reflect changes in core truncal muscle groups. The ability to sit up and the timed supine to sitting test reflects core muscle strength and coordination.
- Hand Function [Baseline - 3 years]
Hand function is captured by examining hand grip strength.
- Timed Up and Go (TUG) [Baseline - 3 years]
Balance and mobility are assessed by using the Timed Up and Go (TUG), a standard outcome measure for the elderly that is also increasingly being used in neuromuscular disorders. Participants are asked to rise from a chair, walk 3 meters, turn 180 degrees and return to a seated position in the chair.
- Saliva Methylation [Baseline - 3 years]
Investigators will isolate DNA from blood cells in saliva - and will determine the methylation levels in the 4q region on chromosome 4 using this new technique. Investigators will compare methylation levels between participants and compare to other clinical information collected in this study.
- FSHD Clinical Severity Scores [Baseline - 3 years]
A limited physical exam and strength testing will be used to derive two FSHD clinical severity scores. These severity scores both rank weakness in the face, shoulders, arms, distal, and proximal lower extremities on either a 10 or 15 point scale. The higher the severity score the more affected the individual.
- Patient-Reported Outcomes Measurement Information System-57 (PROMIS57) [Baseline - 3 years]
The PROMIS57 is an instrument developed by the NIH which generates scores for physical function, and the impact of physical limitations on daily life. 57 questions are summed into a total score, which is transformed into a normalized t-score with 50 representing normal, and lower scores representing increasing disability.
- The Upper Extremity Functional Index [Baseline - 3 years]
This index measures upper extremity dysfunction. 20 questions are combined into a total score, the score is transformed into a normalized score with 80 representing normal, and lower scores representing increasing disability.
- Exercise and Pain Assessment [Baseline - 3 years]
An exercise and pain assessment questionnaire was comprised specifically for this study and will be completed at every visit.
- The Facial Disability Index (FDI) [Baseline - 3 years]
The FDI is a short 5 item questionnaire. The five questions are summed into total score which transformed onto a percentage scale, with 100 representing normal, and lower scores representing increasing disability.
- MIP/MEP and SNIP [Baseline - 3 years]
For sites who routinely obtain negative inspiratory or expiratory force (MIP/MEP) will be collected.
Other Outcome Measures
- Biospecimen Retention: Samples with DNA, RNA, plasma, and serum [Baseline - 3 years]
Optional sub-study collecting DNA, RNA, plasma, and serum for biobanking.
- Remote Assessment Pilot [Baseline - 3 years]
A sub-group of approximately 20 participants will perform remote assessments in the home. The remote assessments are meant to capture the assessments that occur during a routine in-person visit, and will overlap functional categories, to include reaching and lifting objects, core functional measures, measures of gait and balance, and midarm and hand tasks. Measures of respiratory (FVC, FEV1, PCF, SNIP), bulbar function, and handgrip strength will also be included. Functional measures will be modified to allow for independent and/or via two-way video performance.
- MRI [Baseline - 12-Month]
Whole body MRI will be performed for a sub-group of approximately 200 participants. MRI is recognized as a gold standard for body composition analysis, enabling a more complete description of a person's body composition profile from a single examination.In addition, we will include analysis to help make needle biopsy based on STIR and quantitative fat fraction more efficient with higher yield using standard fiducial markings and body landmarks.
- Muscle Biopsy [Baseline - 4-Month]
Muscle biopsy will be be performed for a sub-group of approximately 200 participants. Muscle biopsies will be performed at the baseline visit and for a subset of 20 participants at 4 months. We will use MRI analysis to help inform which lower extremity muscle will be chosen for biopsy. Muscle samples will be used to recapitulate RNA sequencing to confirm prior DUX4 target selection. In addition, other early or late genes of interest may be included which are FSHD-related but not specific to DUX4. We will also select 4 control genes for quality assurance, 2 to confirm muscle tissue, and 2 to rule out high fat content.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Genetically confirmed FSHD (types 1 or 2) or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring.
Exclusion Criteria:
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Unwilling or unable to provide informed consent.
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Any other medical condition which in the opinion of the investigator would interfere with study participation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | David Geffen School of Medicine at UCLA | Los Angeles | California | United States | 90095 |
| 2 | Neuromuscular Disorders Program at Stanford University School of Medicine | Stanford | California | United States | 94306 |
| 3 | University of Colorado Anschutz Medical Campus | Aurora | Colorado | United States | 80045 |
| 4 | Univeristy of Florida Gainesville | Gainesville | Florida | United States | 32608 |
| 5 | Univeristy of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 6 | Kennedy Krieger Institute | Baltimore | Maryland | United States | 21205 |
| 7 | University of Rochester Medical Center | Rochester | New York | United States | 14642 |
| 8 | The Ohio State University Medical Center | Columbus | Ohio | United States | 43221 |
| 9 | Univeristy of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 10 | University of Utah | Salt Lake City | Utah | United States | 84132 |
| 11 | Virginia Commonwealth University | Richmond | Virginia | United States | 23219 |
| 12 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
Sponsors and Collaborators
- University of Kansas Medical Center
- FSHD Society, Inc.
- Friends Research Institute, Inc.
- University of Rochester
- University of Nevada, Reno
- FSHD Canada
- Avidity Biosciences, Inc.
- AMRA Medical
- Seattle Children's Hospital
Investigators
- Principal Investigator: Jeffrey Statland, MD, University of Kansas Medical Center
- Principal Investigator: Rabi Tawil, MD, University of Rochester
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY00145405