Background: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder with no FDA-approved treatment. The disease is caused by the de-repression of the DUX4 gene within the D4Z4 repeat. This genetic anomaly leads to muscle degeneration that significantly impacts this populations quality of life. Clenbuterol, a β2-adrenergic agonist, has shown promise in preclinical studies by inhibiting DUX4 activity in muscle cells derived from FSHD patients and promoting anabolic effects on muscle tissue.
Objective: With this protocol and trial design we hope to determine the optimal dose of clenbuterol that is safe, well-tolerated, reduces DUX4 activity, and increases contractile muscle volume in patients with FSHD.
Methods: This study is part of the NIH Wellstone Grant (P50 AR065139). It is designed as a 6-month, non-randomized, open-label trial conducted at three clinical sites: Kansas City, Rochester, and Seattle. The study will enroll three sequential cohorts of 10 genetically confirmed FSHD patients each. The cohorts will be ascending doses of clenbuterol (20 mcg, 40 mcg, and 60 mcg) administered orally twice daily, and will be monitored for safety, tolerability, and efficacy.
Endpoints: Primary endpoints include safety and tolerability, assessed through adverse event monitoring and clinical evaluations. Secondary endpoints will measure changes in muscle volume using MRI, molecular markers through RNA sequencing, and functional biomarkers.
Expected Outcomes: The study aims to identify the maximum tolerable dose of clenbuterol, characterize its safety profile through potential side effects, and provide preliminary evidence of its efficacy in reducing DUX4 activity while improving muscle function in FSHD patients. The study will provide critical data on the potential of clenbuterol as a therapeutic option for FSHD.
Timeline: Recruitment is anticipated to begin upon receipt of the drug from a third-party vendor in early 2025.