Safety and Preliminary Efficacy of ULSC in Facioscapulohumeral Muscular Dystrophy (FSHD)

Individuals are asked to rise from a chair, walk 3 meters, turn around, return to the chair, and sit. The time that it takes to complete the task will be recorded. The TUG will be performed at a comfortable pace and at a maximum pace. Assistive devices, orthoses, and ankle braces will be allowed. This test involves walking only, not running or skipping. This test is a timed test, and it will use Stanford-created OPENCAP video capture system.

Timed sit to stand tests proximal lower extremity strength and core strength by having subjects stand from a standard height chair. This will be performed and timed one time and five times; the latter using Stanford-created OPENCAP video capture system.

From a standing start, the participant will be asked to go 10 meters either walking at normal speed (10MWT) or as quickly as possible, whether by walking or running (10MWRT). Orthotics and ankle braces are allowed. The time in seconds to complete the task will be recorded; these tests will use Stanford-created OPENCAP video capture system.

Participants will be asked to climb up and down (Timed as separate tests) 4 stairs as quickly as possible, using steps with a six-inch rise and ten-inch run. Quality grades will be captured for this test to record the use of railings and manner of ascent (i.e. step-to or step-over-step pattern). The time it takes to complete the task will be recorded.

Evaluate lower leg and balance by having participants rise onto tip toes as quickly as possible and try and hold it there for 30 seconds. This test will use Stanford-created OPENCAP video capture system.

To evaluate participant's ability to jump as high as possible. If unable to jump, the participant is instructed to simulate a jump by bending their knees and standing upright as fast as they can. This test will use Stanford-created OPENCAP video capture system.

The tasks are an adaptation of the activities contained in the Brooke upper extremity scale, to test straight arm abduction without compensation to lift hands above head, or to test ability to lift a weighted cup (200 g) to chin or alternatively, to lift an unweighted cup. This category tests proximal to mid arm tasks, and the ability to coordinate upper extremity function across a variety of muscle groups (shoulder abduction/flexion, elbow flexion/extension). Brooke score is assigned on scale from 2 (unable to lift unweighted cup from lap to chin) to 6 (hands lifted above head with no compensation). This test will use Stanford-created OPENCAP video capture system.

Measuring the time it takes participants to don and doff a coat, which is a more complex task that incorporates functional use of both proximal and mid-limb muscles.

Assessing participant's ability and number to stack up to five (5) heavy cans.

These tests evaluate right and left separately tested movements including shoulder abduction, shoulder forward flexion, and elbow flexion. Tests will include use of a 5-pound weight and evaluate whether participant can perform movements with full range of motion (ROM) and no compensation for the best score on the scale. In each test, score is determined based on defined criteria, such as the ability to perform with compensation or without weight (antigravity), with or without compensation, or with limited degree of range of motion.

This task evaluates bilateral arm movement in six (6) directions, arm raises in different directions and horizontal sweeps at waist height or as high as able, to assess range of motion of shoulder muscle groups and ability to move arms in smooth controlled way while trying not to bend elbows. This test will use Stanford-created OPENCAP video capture system.

This task evaluates elbow and wrist movement, including elbow full extension, elbow full flexion, and wrist supinated and pronated RoM while keeping elbows at 90° and moving in smooth controlled way. This test will use Stanford-created OPENCAP video capture system.

Picking up a penny or pencil off the floor tests the ability to bend and straighten but also balance and the ability of lower extremity muscles to compensate for core weakness.

The ability to sit up from lying supine and the timed supine to sitting at edge of bed test reflects core muscle strength and coordination. Functional axial strength will be assessed by instructing individuals to move from supine to sitting on the edge of a plinth as quickly as possible. The time that it takes to complete the task will be recorded, as well as the manner of sitting (e.g. using one or two hands to pull up).

QMT will be conducted by trained and study qualified clinical evaluator, with specific procedures as described in the Clinical Evaluator Manual, and using Microfet Handheld Myometer. Shoulder abductors, elbow flexors, elbow extensors, knee flexors, and hand grip force will be evaluated bilaterally and data (kg) will be recorded for each. Each assessment is obtained three times, for 5 seconds each attempt and 10 seconds of rest between each attempt. Every effort should be made to have the same evaluator conduct these tests for an individual participant during the study.

Change from baseline in Muscle Fat Fraction (MFF, %) as a measure of infiltration of fat in muscle; this is assessed by Musculoskeletal (MSK) Magnetic Resonance Imaging (MRI)

Change from baseline in Lean Muscle Volume (LMV, cu cm or Liter) as a measure of infiltration of fat in muscle; this is assessed by Musculoskeletal (MSK) Magnetic Resonance Imaging (MRI).

At prespecified times for at least 30 days, exercise and sleep activity is monitored using the Actigraphy wearable device, providing real-world assessment of physical activity, sleep, functional mobility, and vital signs.

To assess clinical severity of disease on a 10-point scale score, 0 implying no muscle weakness and 10 implying wheelchair dependency.

Change in patient-reported quality of life by using ACTIVLIM 18-item questionnaire (total score scale from 0 to 36) that assess activity limitations of daily living with higher score indicating better function.

Change in patient-reported quality of life by using EQ-5D-5L, which is a standardized measure of health status developed by the EuroQol Group. EQ-5D-5L covers the following five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; the five levels of severity range from no problems to extreme problems. In addition, it provides Visual Analog Scale (VAS) for patient self-assessment of health with VAS 100 score ranging from 0 to 100. Scoring the EQ-5D-5L produces a health state profile index score in which 1 is the best possible health state.

Change in level of disease activity as reflected by patient-reported disease and quality of life outcomes by using Domain Delta 14-item questionnaire, which inquires about the patient's self-assessed perception of change in 14 subdomains including overall health, quality of life, fatigue, pain, subdomains of physical function, and various subdomains that include thinking, satisfaction/performance in social situations, and communication. Participants evaluate their own perceived change on a 5-level scale with scores ranging from "a lot worse" to "a lot better". The Domain Delta is an instrument developed to assess quality of life and how disease has changed since last visit.

Change in level of disease activity as reflected in patient-reported quality of life outcome assessed by using PROMIS-57. The PROMIS-57 is a questionnaire developed by the NIH PROMIS initiative that generates scores for physical function and the impact of physical limitations on daily life.

Change in level of patient-reported pain using Visual Analogue Scale (VAS 10) with 0 being no pain and 10 being the worst pain.

Change in level of disease activity as reflected by patient-reported disease and quality of life outcomes by using UEFI-15. The UEFI-15 is a validated patient reported measure for adults with upper extremity dysfunction involving a 15-item questionnaire that assesses patient-reported level of difficulty in performing activities of daily living using upper extremities and provides a score ranging from 0.0 to 100.0 with 100.0 indicating the highest functional status.

Change in level of disease activity as reflected by patient-reported disease and quality of life outcomes by using FDI. The FDI physical score is a short 5 item questionnaire which assesses the physical impact of facial weakness. The responses are individually scored on a scale of 0 to 5 for physical function, and on a scale of 0 to 6 for social function; total scores that are then converted into a percentage scale. A score of 100% represents normal function with no difficulty or impact, and lower scores indicate increasing levels of disability with higher levels of difficulty and impact.

To evaluate changes from baseline in timed motor function tests.