Clenbuterol to Target DUX4 in FSHD

Phase 1RecruitingNCT06721299

Jeffrey Statland30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Muscular Dystrophy, Facioscapulohumeral

Interventions

ClenbuterolDRUG

Beta-Agonist

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (3)

University of Kansas Medical Center

Kansas City, Kansas, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, United States

RECRUITING

University of Washington

Seattle, Washington, United States

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: from baseline to 6 month visit

change in heart rate

Review of Vitals

Time frame: from Month 1 to Month 6 visit

change in blood pressure

Review of Vitals

Time frame: from Month 1 to Month 6 visit

Safety Lab Potassium (K)

patient safety measured by potassium for signs of hypokalemia

Time frame: Baseline to month 6 visit

Safety Lab Glucose

Patient safety measured by blood glucose abnormalities

Time frame: 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

Time frame: from baseline to 6 month visit

Safety ECG

Looking for sympathomimetic side effects such as cardiac arrhythmias

Time frame: from Month 1 to Month 6 visit

Safety Lab Creatine kinase (CK)

Patient Safety measured by creatine kinase abnormalities

Time frame: Baseline to Month 6 visit

Secondary Outcomes

Central Contacts

Rebecca Clay

CONTACT

9139459936 rclay@kumc.edu

Data from ClinicalTrials.gov

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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.