Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD) (MOVE FSHD)

• ClinicalTrials.gov Identifier: NCT04635891
• Recruitment Status: Recruiting
• First Posted: November 19, 2020
• Last Update Posted: December 14, 2022
• Sponsor: University of Kansas Medical Center
• Collaborators: 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
• Information provided by (Responsible Party): University of Kansas Medical Center

Tracking Information

• First Submitted Date: October 29, 2020
• First Posted Date: November 19, 2020
• Last Update Posted Date: December 14, 2022
• Actual Study Start Date: December 15, 2020
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 13, 2020)

• 10m walk/run [ Time Frame: 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 [ Time Frame: Baseline - 3 years ]
  Range of motion tasks mimicking lifting or reaching up will be performed.
• Shoulder and Arm Function [ Time Frame: Baseline - 3 years ]
  Participants will be timed on stacking cans.
• Spirometry (FVC, FEV1, PCF) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 13, 2020)

• Trunk Function [ Time Frame: 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 [ Time Frame: Baseline - 3 years ]
  Hand function is captured by examining hand grip strength.
• Timed Up and Go (TUG) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: Baseline - 3 years ]
  For sites who routinely obtain negative inspiratory or expiratory force (MIP/MEP) will be collected.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: December 12, 2022)

• Biospecimen Retention: Samples with DNA, RNA, plasma, and serum [ Time Frame: Baseline - 3 years ]
  Optional sub-study collecting DNA, RNA, plasma, and serum for biobanking.
• Remote Assessment Pilot [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline - 4-Month ]
  Muscle biopsy will 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.
• Reachable and Functional Workspace [ Time Frame: Baseline - 24-Months ]
  Reachable and Functional Workspace will be performed for a sub-group of approximately 200 participants. Participants are seated in front of a stereo-camera and perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator. Five-hundred-gram wrist weights will be added. The standardized simple set of movements consist of lifting the arm from the resting position to above the head while keeping the elbow extended, performing the same movement in vertical planes at around 0, 45, 90, 135 degrees. The second set of movements consists of horizontal sweeps at the level of the umbilicus and shoulder. Each set of movements is repeated three times for left and right arm.

Original Other Pre-specified Outcome Measures (submitted: November 13, 2020)

• Biospecimen Retention: Samples with DNA, RNA, and plasma [ Time Frame: Baseline - 3 years ]
  Optional sub-study collecting DNA, RNA, and plasma for biobanking.
• Remote Assessment Pilot [ Time Frame: 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.

Descriptive Information

• Brief Title: Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD)
• Official Title: Motor Outcomes to Validate Evaluations in FSHD (MOVE FSHD)

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

Saliva samples that are collected will be sent to University of Nevada Reno for DNA methylation testing, and participants will receive results. DNA, RNA, plasma, and serum biomarker samples that are collected will be sent to University of Rochester Medical Center and will be stored in a biorepository for future research. Muscle tissue samples that are collected will be sent for RNA sequencing and commercial assay validation. Remaining muscle tissue will be sent to University of Rochester Medical Center biorepository for future research use.

• Sampling Method: Non-Probability Sample

Study Population

Participants with FSHD that are seen in the researchers clinic.

This study is meant to be 'inclusive' and cover the full range of clinical FSHD: including children and adults, all ranges of abilities (ambulatory and non-ambulatory), and both genetic types of FSHD.

• Condition: FSHD
• Intervention: Not Provided

Study Groups/Cohorts

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.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 15, 2021): 450
• Original Estimated Enrollment (submitted: November 13, 2020): 250
• Estimated Study Completion Date: January 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility 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:

• Unwilling or unable to provide informed consent.
• Any other medical condition which in the opinion of the investigator would interfere with study participation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Michaela Walker, MPH; 913-945-9920; mwalker20@kumc.edu

Contact: Leann Lewis, MSGC; 585-275-7680; Leann_Lewis@URMC.Rochester.edu

• Listed Location Countries: Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT04635891
• Other Study ID Numbers: STUDY00145405
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Kansas Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Kansas Medical Center
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: University of Kansas Medical Center
• Verification Date: December 2022