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Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD

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ClinicalTrials.gov Identifier: NCT03458832
Recruitment Status : Active, not recruiting
First Posted : March 8, 2018
Last Update Posted : October 5, 2021
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
University of Kansas Medical Center

Brief Summary:
The primary cause of facioscapulohumeral muscular dystrophy (FSHD), a common adult-onset dystrophy, was recently discovered identifying targets for therapy. As multiple drug companies pursue treatments for FSHD, there is an urgent need to define the clinical trial strategies which will hasten drug development, including creating disease-relevant outcome measures and optimizing inclusion criteria. This proposal will develop two new outcome measures and optimize eligibility criteria by testing 160 patients in 7 sites over a period of 24 months.

Condition or disease Intervention/treatment
Facioscapulohumeral Muscular Dystrophy Diagnostic Test: FSHD-specific functional rating scale Device: Electrical Impedance Myography

Detailed Description:

The overall aim of this study is to hasten drug development for facioscapulohumeral muscular dystrophy (FSHD). Recent breakthroughs in FSHD research have identified the primary disease mechanism as the aberrant expression of a normally silenced gene, DUX4, resulting in a toxic gain-of-function. This disease mechanism is particularly amenable to knock-down of DUX4 using epigenetic strategies or RNA therapies, as well as to other interventions targeting the downstream effects of DUX4 expression. There are many drug companies actively working towards disease-targeted therapies, and two clinical trials either under way now, or planned to start in early Fall 2016. However, meetings with industry, advocacy groups, and FSHD researchers have identified several gaps in the clinical trial arsenal, and clinical trial planning as a major goal for the community. Consequently, there is an urgent need to establish the tools necessary for the conduct of currently planned and expected therapeutic trials in FSHD.

To this end, the researchers propose to develop two novel clinical outcome assessments (COA), a composite functional outcome measure (FSH-COM) and skeletal muscle biomarker, electrical impedance myography (EIM). In addition there is broad consensus a better understanding of the relationship of genetic and demographic features to disease progression will be necessary for enumerating eligibility criteria.

The specific aims are to: 1. Determine the multi-site validity of the COAs, 2. Compare the responsiveness of new COAs to other FSHD outcomes and determine the minimal clinically meaningful changes, and 3. establish FSHD cohort characteristics useful for determining clinical trial eligibility criteria. To achieve these aims, the researchers are conducting a multicenter, prospective, 24 months study of 160 subjects.

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Study Type : Observational
Estimated Enrollment : 160 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD
Actual Study Start Date : March 5, 2018
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Group/Cohort Intervention/treatment
All participants will be asked to undergo FSHD-specific functional rating scale tests and procedures and Electrical Impedance Myography.
Diagnostic Test: FSHD-specific functional rating scale
The FSHD-COM is composed of disease-relevant functional tasks such as leg function; shoulder and arm function; trunk function, hand function, and balance.
Other Name: FSHD-COM

Device: Electrical Impedance Myography
EIM is a non-invasive, painless, and fast technique for obtaining information on how a patient's muscle structure is changing. EIM uses a small electrical current to measure the health of the underlying muscle. The patient will be asked to lie down and a trained clinical evaluator will perform testing on 16 total muscles (8 on each side) on your arms and legs.
Other Name: EIM

Primary Outcome Measures :
  1. Validate FSHD-COM as COA [ Time Frame: 24 Months ]
    The FSHD-COM is an 18-item evaluator-administered instrument comprised of individually validated functional motor tasks. The body regions represented match areas of importance identified by patients and include: leg function; shoulder and arm function; trunk function, hand function; and balance. Each item is scored on a 0-4 scale, with 0 representing unaffected/normal performance, and the divisions based on healthy population normative values, or the relative degree of ability to perform the functional task. The total scale has 72 points, with larger weight given to the two most frequently patient-cited areas of functional motor concern - leg function and shoulder and arm function.

  2. Validate EIM as COA [ Time Frame: 24 Months ]

Secondary Outcome Measures :
  1. Motor Function Measure (MFM) Domain 1 [ Time Frame: 24 Months ]
    The MFM domain 1 is a validated evaluator administered functional measure for neuromuscular disorders, with 13 items related to standing and transfers.

  2. Facial Function [ Time Frame: 24 Months ]
    The Iowa Oral Performance Instrument (IOPI) is a means to quantify lip, tongue, and buccal strength using a validated tool with published ranges for normative data for lingual measurements.

  3. Reachable Workspace [ Time Frame: 24 Months ]
    Subjects are seated in front of a 3D camera and asked to perform a standardized upper extremity movement protocol under the supervision of a study clinical evaluator.

  4. Manual Muscle Testing [ Time Frame: 24 Months ]
    Strength testing will be performed using manual muscle testing (MMT) using a hand held force dynamometer.

  5. Respiratory Function [ Time Frame: 24 Months ]
    The researchers will obtain forced vital capacity and forced expiratory volume in 1 second using bedside spirometry.

  6. Whole body and regional lean muscle mass (LMM) [ Time Frame: 24 Months ]
    Whole body and regional lean muscle mass (LMM) will be measured via Dual Energy X-Ray Absorptiometry (DEXA).

  7. Severity Scores [ Time Frame: 24 Months ]
    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.

  8. FSHD-Health Inventory (HI) [ Time Frame: 24 Months ]
    The HI is a 15 domain questionnaire designed and based on patient interviews to measure total FSHD health-related quality-of-life, including both motor impairment and the social and emotional impact of FSHD. 116 questions are combined into a total score, the score is transformed onto a percentage scale, with 100 representing maximal disability, and lower scores representing decreasing disability.

  9. Patient-Reported Outcomes Measurement Information System-57 (PROMIS57) [ Time Frame: 24 Months ]
    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.

  10. The Upper Extremity Functional Index [ Time Frame: 24 Months ]
    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.

  11. The Facial Disability Index (FDI) [ Time Frame: 24 Months ]
    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.

  12. Fall assessment [ Time Frame: Total between Month 3 and Month 6 Visit ]
    Fall assessment will be completed weekly for 3 months after the month 3 visit.

  13. Quantitative myometry [ Time Frame: 24 Months ]
    Force will be measured on digital myometer, in KG-force.

Biospecimen Retention:   Samples With DNA
Each subject will have approximately 15 mL of blood collected at baseline and month 3 for genetic testing. The month 3 sample will be stored for use as a back-up for any lost samples, or for use in future studies.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants with FSHD that are seen in the researchers clinic.

Inclusion Criteria:

  • Patients with genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring
  • Patients with symptomatic limb weakness
  • Patients must be able to walk 30 feet without the support of another person or assistance (canes, walking sticks, and braces allowed; no walker).
  • If taking over the counter supplements, willing to remain consistent with supplement regimen throughout the course of the study

Exclusion Criteria:

  • Patients with cardiac or respiratory dysfunction (deemed clinically unstable, or would interfere with safe testing, in the opinion of the Investigator)
  • Patients with orthopedic conditions that preclude safe testing of muscle function
  • Patients that regularly use available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists
  • Patients that have used an experimental drug in an FSHD clinical trial within the past 30 days
  • Patients that are pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03458832

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United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Kansas Medical Center
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Jeffrey Statland, MD University of Kansas Medical Center
Principal Investigator: Rabi Tawil, MD University of Rochester
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT03458832    
Other Study ID Numbers: STUDY00140842
U01NS101944 ( U.S. NIH Grant/Contract )
First Posted: March 8, 2018    Key Record Dates
Last Update Posted: October 5, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Kansas Medical Center:
muscular dystrophy.
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Facioscapulohumeral
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn