Clenbuterol to Target DUX4 in FSHD (Target FSHD)

Clenbuterol to Target DUX4 in FSHD (Target FSHD): Open Label Safety and Tolerability Study of 3 Doses of Clenbuterol

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.

Study Overview

• Status: Recruiting
• Conditions: Muscular Dystrophy, Facioscapulohumeral
• Intervention / Treatment: Drug: Clenbuterol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rebecca Clay; Phone Number: 9139459936; Email: rclay@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
      • Principal Investigator: Jeffrey Statland
      • Contact: Rebecca Clay, BS; Phone Number: 913-945-9936; Email: rclay@kumc.edu
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Leann Lewis, MSGC; Phone Number: 585-275-7680; Email: Leann_Lewis@URMC.Rochester.edu
      • Principal Investigator: Brianna Brun
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • University of Washington
      • Contact: Lilly Young; Phone Number: 206-616-5957; Email: eyoung8@uw.edu
      • Contact: Leo Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Genetically confirmed diagnosis of FSHD type 1 or 2, or have a clinical diagnosis of FSHD type 1 with a first degree relative with confirmed mutation
• between 18 and 75 years of age
• with a clinical severity score between 0 and 10
• Able to walk 30ft without support of another person
• Showing anti-gravity strength on at least one of the tibialis anterior muscles or having an MRI eligible muscle in the leg for needle biopsy
• willing and able to provide informed consent
• agree to follow the contraceptive requirement for duration of the study

Exclusion Criteria:

• Pregnant or planning to become pregnant during the conduct of the study
• have a poorly controlled medical condition
• Were involved in a study of an experimental agent within 3 months of enrollment
• Are taking beta-blockers or anabolic agent or potassium wasting diuretics
• Are taking or are planning to take a GLP-1 Agonist during trial
• have any condition or contraindication which would interfere with testing or preclude use of beta-agonist
• Are taking blood thinners or medications which make a needle muscle biopsy contra-indicated
• Has contraindication to lactose such as galactosmia, lactase deficiency and glucose-galactose malabsorption. For those who are lactose intolerant, the PI will determine acceptability based on tolerance reaction to lactose
• Are taking any medications or therapies with a contraindication to Clenbuterol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clenbuterol Cohort 1; 20 mcg taken orally twice daily	Drug: Clenbuterol; Beta-Agonist
Experimental: Clenbuterol Cohort 2; 40 mcg taken orally twice daily	Drug: Clenbuterol; Beta-Agonist
Experimental: Clenbuterol Cohort 3; 60 mcg taken orally twice daily	Drug: Clenbuterol; Beta-Agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	Patient Safety measured by creatine kinase abnormalities	Baseline to Month 6 visit

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Jeffrey Statland
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); University of Washington; University of Rochester

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: September 5, 2024
• First Submitted That Met QC Criteria: December 5, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: FSHD
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Facioscapulohumeral; Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Clenbuterol
• Other Study ID Numbers: STUDY00150777; P50AR065139 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No