Clinical Trial Readiness to Solve Barriers to Drug Development in FSHD
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 324
- 试验地点
- 20
- 主要终点
- Electrical Impedance Myography (EIM)
研究概览
简要总结
The primary cause of facioscapulohumeral muscular dystrophy (FSHD), a common adult-onset dystrophy, was recently discovered identifying targets for therapy. As multiple drug companies pursue treatments for FSHD, there is an urgent need to define the clinical trial strategies which will hasten drug development, including creating disease-relevant outcome measures and optimizing inclusion criteria. This proposal will develop two new outcome measures (FSHD-COM and EIM) and optimize eligibility criteria by testing 320 patients across 14 international sites over a period of 24 months.
详细描述
The overall aim of this study is to hasten drug development for facioscapulohumeral muscular dystrophy (FSHD). Recent breakthroughs in FSHD research have identified the primary disease mechanism as the aberrant expression of a normally silenced gene, DUX4, resulting in a toxic gain-of-function. This disease mechanism is particularly amenable to knock-down of DUX4 using epigenetic strategies or RNA therapies, as well as to other interventions targeting the downstream effects of DUX4 expression. There are many drug companies actively working towards disease-targeted therapies, and two clinical trials either under way now, or planned to start in early Fall 2016. However, meetings with industry, advocacy groups, and FSHD researchers have identified several gaps in the clinical trial arsenal, and clinical trial planning as a major goal for the community. Consequently, there is an urgent need to establish the tools necessary for the conduct of currently planned and expected therapeutic trials in FSHD.
To this end, the researchers propose to develop two novel clinical outcome assessments (COA), a composite functional outcome measure (FSHD-COM) and skeletal muscle biomarker, electrical impedance myography (EIM). In addition, there is broad consensus a better understanding of the relationship of genetic and demographic features to disease progression will be necessary for enumerating eligibility criteria.
The specific aims are to: 1. Determine the multi-site validity of the COAs, 2. Compare the responsiveness of new COAs to other FSHD outcomes and determine the minimal clinically meaningful changes, and 3. establish FSHD cohort characteristics useful for determining clinical trial eligibility criteria. To achieve these aims, the researchers are conducting a multicenter, prospective, 24 months study of 320 subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients with genetically confirmed FSHD1 or clinical diagnosis of FSHD with characteristic findings on exam and an affected parent or offspring
- •Patients with symptomatic limb weakness
- •Patients must be able to walk 30 feet without the support of another person or assistance (canes, walking sticks, and braces allowed; no walker).
- •If taking over the counter supplements, willing to remain consistent with supplement regimen throughout the course of the study
排除标准
- •Patients with cardiac or respiratory dysfunction (deemed clinically unstable, or would interfere with safe testing, in the opinion of the Investigator)
- •Patients with orthopedic conditions that preclude safe testing of muscle function
- •Patients that regularly use available muscle anabolic/catabolic agents such as corticosteroids, oral testosterone or derivatives, or oral beta agonists
- •Patients that have used an experimental drug in an FSHD clinical trial within the past 30 days
- •Patients that are pregnant
研究组 & 干预措施
FSHD-COM
All participants will be asked to undergo FSHD-specific functional rating scale tests and procedures and Electrical Impedance Myography.
干预措施: FSHD-specific functional rating scale (Diagnostic Test)
FSHD-COM
All participants will be asked to undergo FSHD-specific functional rating scale tests and procedures and Electrical Impedance Myography.
干预措施: Electrical Impedance Myography (Device)
结局指标
主要结局
Electrical Impedance Myography (EIM)
时间窗: 24 Months
EIM is administered using an investigational device manufactured by Skulpt, Inc (Boston, MA) that non-invasively measures the impedance of skeletal muscle over a frequency range between 1 kHz and 10 MHz (Figure 2). The impedance is measured at each frequency by applying low-intensity electrical current (\<1 mA) via surface electrodes and measuring the resulting voltage signals using a second set of surface electrodes, converting them into 2 impedance parameters, the resistance and the reactance.
FSHD composite (FSHD-COM)
时间窗: 24 Months
The FSHD composite (FSHD-COM) is an 18-item evaluator-administered instrument comprised of individually validated functional motor tasks. The body regions represented match areas of importance identified by patients and include: leg function; shoulder and arm function; trunk function, hand function; and balance. Each item is scored on a 0-4 scale, with 0 representing unaffected/normal performance, and the divisions based on healthy population normative values, or the relative degree of ability to perform the functional task. The total scale has 72 points, with larger weight given to the two most frequently patient-cited areas of functional motor concern - leg function and shoulder and arm function.
次要结局
- Manual Muscle Testing (MMT)(24 Months)
- Quantitative myometry (QMA)(24 Months)
- Motor Function Measure (MFM) Domain 1(24 Months)
- Reachable Workspace (RWS)(24 Months)
- Force Vital Capacity (FVC)(24 Months)
- Fall assessment(Total between Month 3 and Month 6 Visit)
- Whole body and regional lean muscle mass (LMM)(24 Months)
- Severity Scores(24 Months)
- FSHD-Health Inventory (HI)(24 Months)
- The Upper Extremity Functional Index(24 Months)
- Domain Delta Anchor(24 Months)
- Facial Function(24 Months)
- Blood biomarkers(24-Months)
- Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP)(24 Months)
- Patient-Reported Outcomes Measurement Information System-57 (PROMIS57)(24 Months)
- The Facial Disability Index (FDI)(24 Months)
- Muscle Biopsy(24 Months)