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| ID | Type | Description | Link |
|---|---|---|---|
| P50AR065139 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Washington | OTHER |
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
| University of Rochester | OTHER |
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The purpose of this study is to determine if Clenbuterol is a therapeutic option for FSHD by determining the safety and tolerability of the medication at three different dose levels.
Clenbuterol is an EMA approved drug for COPD that three independent patient derived screens identified as suppressing DUX4 expression in cultured FSHD muscle. Prior clinical studies with related beta2-agonists showed some activity in FSHD but did not meet their primary endpoint, although the prior studies would likely have been designed differently with current knowledge. Target FSHD is a 6-month open-label multiple ascending dose study of clenbuterol for safety and tolerability to determine the best dose for a future trial of efficacy. In addition, this study will collect secondary outcome data on muscle function, MRI changes (lean muscle volume, fat infiltration, STIR-rating) and molecular markers of disease activity (histopathology and pre-determined baskets of DUX4-target, inflammation, and ECM genes) at the beginning and end of the study to assess and power their utility as measures of drug activity in a future interventional study of efficacy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clenbuterol Cohort 1 | Experimental | 20 mcg taken orally twice daily |
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| Clenbuterol Cohort 2 | Experimental | 40 mcg taken orally twice daily |
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| Clenbuterol Cohort 3 | Experimental | 60 mcg taken orally twice daily |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clenbuterol | Drug | Beta-Agonist |
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| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Clenbuterol-related adverse reactions | Patient report and medical records will be used to document adverse events and severe adverse events. Adverse events and severe adverse events will be assessed by the investigator and reported as needed for safety. | from baseline to 6 month visit |
| change in heart rate | Review of Vitals | from Month 1 to Month 6 visit |
| change in blood pressure | Review of Vitals | from Month 1 to Month 6 visit |
| Safety Lab Potassium (K) | patient safety measured by potassium for signs of hypokalemia | Baseline to month 6 visit |
| Safety Lab Glucose | Patient safety measured by blood glucose abnormalities | Baseline to month 6 visit |
| Tolerability of 3 doses of clenbuterol in sequential cohorts | Tolerability will be defined as completing an arm without any clenbuterol related adverse events causing someone to withdraw | from baseline to 6 month visit |
| Safety ECG | Looking for sympathomimetic side effects such as cardiac arrhythmias | from Month 1 to Month 6 visit |
| Safety Lab Creatine kinase (CK) |
| Measure | Description | Time Frame |
|---|---|---|
| MRI | MRI measurements are considered gold standard for lean muscle volume measurement and disease biomarkers (fat volumes, fat faction, and STIR+ presence) that may be modulated by treatment. 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. | Screening to Month 6 Visit |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rebecca Clay | Contact | 9139459936 | rclay@kumc.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Recruiting | Kansas City | Kansas | 66160 | United States |
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| ID | Term |
|---|---|
| D020391 | Muscular Dystrophy, Facioscapulohumeral |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D002976 | Clenbuterol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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Three sequential multiple ascending dose cohorts (of n=10 participants)
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Patient Safety measured by creatine kinase abnormalities |
| Baseline to Month 6 visit |
| Muscle Biopsy for RNA sequencing | change in a set of DUX4-regulated genes as measured in muscle using RNA sequencing. goal is to better understand the molecular changes in muscle tissue effected by the use of Clenbuterol. | Baseline and Month 6 |
| FSHD-COM | An 18-item evaluator administered instrument comprised of individually validated functional motor task.the body regions assessed match areas of importance identified by patients and include leg function; shoulder and arm function; trunk function, hand function; and functional balance | Screening to Month 6 Visit |
| Manual Muscle Testing (MMT) | a modified Medical Research Council 13-point scale with standardized positions for each muscle will help look at subject's change in strength over time. | Screening to Month 6 Visit |
| Quantitative Muscle Testing (QMT) | Will test 5 bilateral muscles using a fixed myometry testing system with a force transducer attached by an inelastic strap to a metal frame, This will help us assess subjects change in strength | Screening to Month 6 Visit |
| Patient Reported Outcome Measurement Information System-57 (Promis57) | 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. | Screening to Month 6 Visit |
| FSHD Rasch-built overall disability scale (FSHD-RODS) | The FSHD-RODS is a questionnaire about the relationship between daily activities and health. 32 questions are are constructed using a modern clinimetric technique, the Rasch analysis, which by ordering the items in increasing difficulty, allows for the calculation of the sum of item scores to achieve a total score. Answers provide information about how FSHD affects daily and social activities and to what degree participants are able to perform usual activities. | Screening to Month 6 Visit |
| Upper Extremity Functional Index (UEFI) | 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. | Screening to Month 6 visit |
| Clinical Global Impression of Severity and Change (CGI-S and CGI-C) | Is a rating scale that measures symptom severity and change in severity in response to treatment in clinical trials. | Screening to Month 6 visit |
| University of Rochester Medical Center | Recruiting | Rochester | New York | 14642 | United States |
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| University of Washington | Recruiting | Seattle | Washington | 98104 | United States |
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| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000588 |
| Amines |