Biomarker Development in LGMD2i
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 11
- 主要终点
- 10-Meter walk (10 MWT) -mobility
研究概览
简要总结
The overall goal of this natural history study is to define the key LGMD2i phenotypes as measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker for LGMD2i to support therapeutic development.
详细描述
Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due to missense mutations in the Fukutin-related protein (FKRP) gene. Patients develop progressive proximal muscle weakness that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and respiratory compromise.
There are promising new therapies that have been developed and as a result therapeutic trials are approaching.
The rationale for this study is to define appropriate COAs for LGMD2i, which will facilitate therapeutic development and ensure properly powered clinical trials. In addition, measurement of dystroglycan in muscles represents a potential muscle biomarker that could be used in early phase clinical trials as a measure of target engagement. The clinical utility of changes in dystroglycan has not been validated in human samples.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 10 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 10-65 at enrollment
- •Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity)
- •A genetically confirmed mutation in FKRP (LGMD2i)
- •Willing and able to give informed consent and follow all procedures and requirements
排除标准
- •Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.
- •History of a bleeding disorder, platelet count <50,000, current use of an anticoagulant.
- •Positive pregnancy test
- •A 10-meter walk time of <4 seconds
结局指标
主要结局
10-Meter walk (10 MWT) -mobility
时间窗: Through study completion at 12 months
The 10 MWT will be used to determine the ambulatory Cohort for of all subjects. For the purposes of this study, the definitions for ambulation are as follows: * Cohort A: completes the 10 MWT unaided in ≥ 4 to ≤ 12 seconds * Cohort B: completes the walk unaided in \> 12 seconds or is non-ambulatory
FVC - Pulmonary function
时间窗: Through study completion at 12 months
The total amount of air exhaled during the forced expiratory volume test (Forced vital capacity - FVC) will be assessed in a sitting position only.
Hand Held Dynamometry (HHD) - isometric strength
时间窗: Through study completion at 12 months
HHD using the MicroFET2 myometer will be utilized to capture isometric strength in target muscle groups. Maximum strength in kilograms will be reported for each muscle group provided a continuous scale variable for analysis.
100-Meter Timed Test (100m) - mobility
时间窗: Through study completion at 12 months
The 100m timed test is designed to capture maximal ambulatory capacity. The participant will be asked to complete 4 full laps around 2 cones set 25 meters apart as quickly and as safely as possible, including running if able. This will not be assessed in participants with a 10-meter walk time greater than 12 seconds.
9 Hole Peg Test (9HPT) - distal upper extremity function
时间窗: Through study completion at 12 months
The 9HPT is a quantitative measure of distal upper extremity function. It measures the time required for patients to place 9 pegs in the 9 holes on the board and then remove them as quickly as possible.
NSAD- Motor performance
时间窗: Through study completion at 12 months
North Star Assessment for Dysferlinopathy (NSAD) is a functional scale specifically designed to measure motor performance in individuals with LGMD. It consists of 29 items that are considered clinically relevant items from the North Star Ambulatory Assessment and the Motor Function Measure 20 with a maximum score of 54 and higher scores indicate higher functional abilities.
Timed up-and-go (TUG) - mobility
时间窗: Through study completion at 12 months
The TUG is an assessment used to evaluate functional ambulation, balance, and fall risk. The fastest time to rise from a chair, walk 3 meters, and return to sitting independently without an assistive device will be recorded. This will not be assessed in Cohort B participants.
Performance of Upper Limb (PUL 2.0) - limb function
时间窗: Through study completion at 12 months
The PUL is a tool designed for assessing upper limb function in persons with neuromuscular disorders. It was developed as a conceptual framework reflecting the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy (DMD). There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest.
Timed 4 stair Climb (4SC) - mobility
时间窗: Through study completion at 12 months
The 4SC quantifies the time required for the participant to ascend 4 standard steps. This will not be assessed in participants with a 10 meter walk time greater than 12 seconds.
次要结局
- To develop clinical outcome assessments for LGMD2i(Through study completion at 12 months)