Clenbuterol to Target DUX4 in FSHD (Target FSHD): Open Label Safety and Tolerability Study of 3 Doses of Clenbuterol
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Frequency of Clenbuterol-related adverse reactions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Clenbuterol Cohort 3
60 mcg taken orally twice daily
干预措施: Clenbuterol (Drug)
Clenbuterol Cohort 2
40 mcg taken orally twice daily
干预措施: Clenbuterol (Drug)
Clenbuterol Cohort 1
20 mcg taken orally twice daily
干预措施: Clenbuterol (Drug)
结局指标
主要结局
Frequency of Clenbuterol-related adverse reactions
时间窗: from baseline to 6 month visit
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.
change in heart rate
时间窗: from Month 1 to Month 6 visit
Review of Vitals
change in blood pressure
时间窗: from Month 1 to Month 6 visit
Review of Vitals
Safety Lab Potassium (K)
时间窗: Baseline to month 6 visit
patient safety measured by potassium for signs of hypokalemia
Safety Lab Glucose
时间窗: Baseline to month 6 visit
Patient safety measured by blood glucose abnormalities
Tolerability of 3 doses of clenbuterol in sequential cohorts
时间窗: from baseline to 6 month visit
Tolerability will be defined as completing an arm without any clenbuterol related adverse events causing someone to withdraw
Safety ECG
时间窗: from Month 1 to Month 6 visit
Looking for sympathomimetic side effects such as cardiac arrhythmias
Safety Lab Creatine kinase (CK)
时间窗: Baseline to Month 6 visit
Patient Safety measured by creatine kinase abnormalities
次要结局
- MRI(Screening to Month 6 Visit)
- Muscle Biopsy for RNA sequencing(Baseline and Month 6)
- FSHD-COM(Screening to Month 6 Visit)
- Manual Muscle Testing (MMT)(Screening to Month 6 Visit)
- Quantitative Muscle Testing (QMT)(Screening to Month 6 Visit)
- Patient Reported Outcome Measurement Information System-57 (Promis57)(Screening to Month 6 Visit)
- FSHD Rasch-built overall disability scale (FSHD-RODS)(Screening to Month 6 Visit)
- Upper Extremity Functional Index (UEFI)(Screening to Month 6 visit)
- Clinical Global Impression of Severity and Change (CGI-S and CGI-C)(Screening to Month 6 visit)
研究者
Jeffrey Statland
Professor of Neurology
University of Kansas Medical Center