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
|Condition or disease||Intervention/treatment|
|Facioscapulohumeral Muscular Dystrophy||Diagnostic Test: FSHD-specific functional rating scale Device: Electrical Impedance Myography|
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.
|Study Type :||Observational|
|Estimated Enrollment :||160 participants|
|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|
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
- 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.
- Validate EIM as COA [ Time Frame: 24 Months ]
- 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.
- 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.
- 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.
- Manual Muscle Testing [ Time Frame: 24 Months ]Strength testing will be performed using manual muscle testing (MMT) using a hand held force dynamometer.
- Respiratory Function [ Time Frame: 24 Months ]The researchers will obtain forced vital capacity and forced expiratory volume in 1 second using bedside spirometry.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Quantitative myometry [ Time Frame: 24 Months ]Force will be measured on digital myometer, in KG-force.
Biospecimen Retention: Samples With DNA
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
|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|
|Principal Investigator:||Jeffrey Statland, MD||University of Kansas Medical Center|
|Principal Investigator:||Rabi Tawil, MD||University of Rochester|