A Monocentre, Prospective, Longitudinal and Observational Natural History Study for Patients With Nemaline Myopathy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Change in Motor Function Measure (MFM32) Score
研究概览
简要总结
This is a prospective, longitudinal, observational study designed to characterize the natural history of Nemaline Myopathy (NM), a rare congenital neuromuscular disorder. The study will follow up to 10 participants of any age with genetically confirmed NM over a period of three years. Data will be collected during routine annual hospital visits and include clinical, motor, respiratory, and quality-of-life assessments. The goal is to improve clinical trial readiness by identifying disease-specific outcome measures and potential biomarkers.
详细描述
Nemaline Myopathies (NM) are a group of rare, genetically and clinically heterogeneous congenital myopathies characterized by the presence of nemaline bodies (rods) on muscle biopsy. The estimated incidence is approximately 1 in 50,000, though this is likely underestimated due to phenotypic variability and underdiagnosis of milder forms. NM typically presents in childhood, but adult-onset cases have been reported, often with retrospectively recognized early symptoms. Clinical manifestations range from severe neonatal presentations requiring mechanical ventilation, to milder forms compatible with ambulation and normal lifespan. Common features include congenital hypotonia, bulbar and respiratory involvement, and proximal muscle weakness, with sparing of extraocular muscles.
NM is associated with mutations in at least 12 genes, including NEB and ACTA1, which account for the majority of genetically confirmed cases. Inheritance patterns can be autosomal dominant or recessive. Despite advances in genetic diagnostics, a subset of patients remains without a confirmed molecular diagnosis.
Currently, treatment is supportive and aligned with general standards of care for congenital myopathies. However, several therapeutic strategies are in preclinical development, targeting gene-specific mechanisms, muscle function, and myogenesis. Clinical translation is challenged by disease rarity, heterogeneity, and the lack of validated outcome measures and biomarkers.
This monocentric study aims to address these gaps by prospectively observing up to 10 patients with NM over three years. Study assessments will coincide with routine annual hospital visits to minimize participant burden. For participants under 18 years of age, additional assessments at 6 and 18 months will be conducted to capture developmental changes.
Data collection will include:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female
- •Patient and/or parent or legal guardian must be willing and have the ability to provide written informed consent for participation in the study.
- •Diagnosis of NM which in most cases includes having a disease-causing variant/s in one of the known NM causative genes and a consistent clinical phenotype.
排除标准
- •Any confirmed chronic or acute condition or disease affecting any system(s), which could interfere with the results of the study and/or the compliance with the study procedures. This will be subject to the clinical judgement of the Coordinating Investigator (CI) and/or the Principal Investigator (PI).
- •Clinically significant medical finding on the physical examination other than NM that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the study procedures.
- •Participants of ongoing (interventional) clinical trials that assess the efficacy of potential treatments will be excluded as assessments need to be done on the basis that represent the natural progression of NM.
- •Safety concerns. This includes anything that might put the participant and/or their Parent(s) or Guardian(s) at risk through participating in the study potentially including but not limited to: Safeguarding concerns, Social Issues and Health issues.
- •Ongoing pregnancy (for participants becoming pregnant during the trial, some assessments may be cancelled or postponed. This will be subject to the clinical judgement of the Coordinating Investigator and/or the Principal Investigator)
结局指标
主要结局
Change in Motor Function Measure (MFM32) Score
时间窗: Over 3 years
Difference in MFM32 score from baseline to each follow-up visit. The MFM32 is a validated scale (range 0-96; higher scores indicate better motor function).
Change in Ventilation Hours per Day
时间窗: Over 3 years
Evolution of the number of hours of assisted ventilation per day compared to baseline.
次要结局
- Change in Quality of Life Score (PROMIS-29 Profile v2.1)(Over 3 years)
- Drop-out Rate(Over 3 years)
研究者
Manon HUSTINX
Principal Investigator, Neurologist
Centre Hospitalier Universitaire de Liege