A Registered Observational Cohort Study of Dysferlinopathy in China
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Clinical status of patients with dysferlinopathy (MMT score)
研究概览
简要总结
The cohort data to be collected aims to evaluate the phenotype, disease progression, natural history, as well as molecular, genetic, and morphological characteristics of dysferlinopathies (LGMD2B/Miyoshi) in China, contributing to the development of clinical outcome measures and the identification of potential biomarkers for future clinical trials.
详细描述
Dysferlinopathy is an autosomal recessive myopathy caused by mutations in the DYSF gene. Dysferlinopathy represents a rare group of muscular dystrophies, characterized by the "core" phenotypes of Miyoshi Myopathy (MM), Limb-Girdle Muscular Dystrophy Type R2 (LGMDR2) and the rarer distal myopathy with anterior tibial involvement. As the disease progresses, involvement of both proximal and distal muscles is observed in many patients, deviating from the classic muscle weakness patterns of LGMD2B or Miyoshi Myopathy. In addition, the age at onset and the progression of muscle weakness exhibit considerable heterogeneity among patients. Compared to other types of muscular dystrophy, dysferlinopathy exhibits variable onset ages for wheelchair dependency and likely carries a lower risk of cardiac and respiratory complications. Therefore, detailed and regular assessments of motor function, along with follow-up, are essential for systematically understanding the disease progression and natural history of dysferlinopathy, as well as for providing data to support future clinical trials.
Dysferlinopathy is characterized by typical dystrophic pathological changes, including necrosis and regeneration of muscle fibers, hypertrophy and atrophy, as well as proliferation of connective tissue. The absence of DYSF protein expression on the sarcolemma is a key pathological hallmark and diagnostic criterion of dysferlinopathy. Moreover, inflammatory infiltration represents a significant pathological feature of this condition. Specific analysis of the immune environment in skeletal muscles may serve as a potential therapeutic target for dysferlinopathy in future research.
The Chinese dysferlinopathy patient registry is a nationwide, population-based observational cohort study encompassing dysferlinopathy patients across all age groups, collecting retrospective data at study entry and prospective data during follow-up. This registry is intended to contribute to the development of clinical outcome measures and the identification of potential biomarkers for future clinical trials.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients of all ages at baseline.
- •Confirmed diagnosis of dysferlinopathy proven by i) two (predicted) pathogenic variations in DYSF gene, ii) one (predicted) pathogenic variation plus either absent dysferlin protein expression on muscle immunoblot. Mutations will be checked for pathogenicity via the UMD bioinformatics tools and and by checking the literature and mutation /variant databases.
- •Ambulant with or without aids; or full-time wheelchair user, i.e. non-ambulant; with the ratio 2:1 between recruited ambulant and recruited non-ambulant patients.
- •Ability to perform assessments (there will be different assessments for ambulant and non-ambulant patients).
- •Informed consent to participate in the study.
排除标准
- •Decline to participate.
- •Other neuromuscular disease (such as Duchenne/Becker muscular dystrophy or Myotonic dystrophy).
- •Serious systemic illness (such as cute cardiac, renal, hepatic insufficiency, myocardial infarction or an acute cerebrovascular accident (stroke) as well as infectious diseases).
结局指标
主要结局
Clinical status of patients with dysferlinopathy (MMT score)
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 years
Muscle strength will be assessed using MMT and will be expressed in points for each of the muscle groups assessed. Data will be reported from 0 to 5, with lower score pointing to weaker muscle strength.
North Star assessment for limb girdle-type muscular dystrophies (NSAD) in patients with dysferlinopathy
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 years
A functional scale that will be used to measure motor performance in individuals with LGMD. Data will be reported from 0 to 54, with lower score pointing to worse motor performance.
Clinical status of patients with dysferlinopathy (6-minute walk test)
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 years
The participant will be asked to complete maximal distance in 6 minute as quickly as safely possible and the time in seconds is recorded.
次要结局
- Muscle MRI in patients with dysferlinopathy(At baseline and during patients visits and follow-up through study completion, an average of 1 year.)
- Muscle pathology analysis in patients with dysferlinopathy (dysferlin and inflammatory infiltration detection )(Conducted with informed consent at baseline.)
研究者
Meng YU
Dr.
Peking University First Hospital