A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy: the Extended LAST STRONG Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change of Motor Function Measure (MFM)-32 (older than 7 years) of MFM-20 (2 to 7 years old)
研究概览
简要总结
SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD) are congenital neuromuscular disorders presenting with slowly, progressive axial muscle weakness, spinal rigidity, scoliosis and respiratory insufficiency. Currently, no curative treatment options exist, yet promising preclinical trials are ongoing. Clinical trials are expected to start within 5 years. Natural history data and outcome measures for measuring therapy effectiveness were lacking. Therefore, the LAST STRONG Study (a 1.5-year natural history study) started in 2020. With the extended LAST STRONG Study, we aim to further analyze and expand the 1.5-year natural history data on SELENON-RM or LAMA2-MD to provide a detailed clinical description of the Dutch and Flemish cohort. This will enable a smooth transition towards implementation into clinical care and clinical trials.
The extended LAST STRONG Study is a prospective, observational natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM and LAMA2-MD. Patients will be invited to visit our hospital two times (3- and 5-years) after the first visit in the LAST STRONG Study. During both visits, patients will undergo a subset of tests (neurological examination, functional measurements, questionnaires, muscle ultrasound, MRI, pulmonary assessment and accelerometry). All measurements are adapted to the patient's age and functional disabilities.
详细描述
Rationale: A long-term prospective natural history study in an unselected group of patients including clinical and functional outcome measures is lacking in both SELENON-related myopathy (SELENON-RM) and LAMA2-related muscular dystrophy (LAMA2-MD). Due to the promising ongoing preclinical trials, there is a high need to obtain natural history data in order to reach trial readiness for both diseases. With the extended LAST STRONG study, we aim to further analyze and expand our 1.5-year natural history data on SELENON-RM and LAMA2-MD to provide a detailed clinical description of the Dutch and Flemish cohort. This will enable a smooth transition towards implementation into clinical care and clinical trials that are expected to start within 5 years.
Objective
(1) To collect 3- and 5-year natural history data in patients with SELENON-RM and LAMA2-MD. (2) Implementation of natural history data collection into clinical care and international guidelines, and reach trial readiness.
Study design: This is an observational study. A variety of tests will be performed to get a full impression of the patient's abilities and disabilities (standard medical history, neurological examination, functional measurements, questionnaires, imaging, pulmonary assessment and accelerometry). The tests that the patient undergoes depend on the age/abilities/wishes. The tests are selected based on our previously performed 1.5-year natural history study in LAMA2-MD and SELENON-RM. Each participant will perform these measurements during the two scheduled visits at 3- and 5-year after the first visit during the LAST STRONG Study.
Risk and benefit assessment: This study does not concern any product (medicinal product, food product or medical device). There is a small risk for minor injury, e.g. when a participant falls. However since the investigators use all functional tests using movements to which most participants are familiar (i.e. walking, transfers, etc.), the participant will be able to estimate his/her own risk. The investigators don't include tests in which they push participants to their physical limits. the investigators conclude that this study has a negligible risk. A benefit includes the possibility for participants to get a detailed analysis on their own health. Additionally, participants will contribute to the design of future clinical trials on possible treatment options.
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
- 1 Day 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to complete (part of) the measurement protocol at the Radboudumc, Nijmegen. If patients do not wish or not able to visit our neuromuscular center, they are offered to participate in our study through home visits.
- •Genetic conformation of LAMA2-related muscular dystrophy or SELENON-related myopathy by two recessive (likely) pathologic mutations in the LAMA2 or SELENON gene.
- •Typical clinical and histological characteristics combined with genetic confirmation in a first degree relative.
- •Dutch speaking
排除标准
- •Insufficient understanding of the Dutch language
结局指标
主要结局
Change of Motor Function Measure (MFM)-32 (older than 7 years) of MFM-20 (2 to 7 years old)
时间窗: Change from baseline to 3 years and 5 years
Global motor functioning. The items of the MFM are classified in 3 domains: D1: standing and transfers, D2: Axial and proximal motor function, D3: Distal motor function. Higher scored indicate a better outcome. The range of the total score is 0-96. The main point of interest includes the change of MFM score over a period of 5 years.
次要结局
- Change of The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score (children under the age of 2 years)(Change from baseline at 3 years and 5 years)
- Change of Impact on Participation and Autonomy (IPA) (18 years and older)(Change from baseline at 3 years and 5 years)
- Change of maximal voluntary isometric contraction (5 years and older)(Change from baseline at 3 years and 5 years)
- Change of fatigue (pediatric 2-17 years old) assessed by PedsQL Multidimensional Fatigue Scale (MFS)(Change from baseline at 3 years and 5 years)
- Change of physical activity in daily life assessed by an accelerometer (GENEActiv original devices) for 7 days(Change from baseline to 3 years and 5 years)
- Change of Hammersmith Infant Neurological Examination (HINE) (under the age of 2 years)(Change from baseline at 3 years and 5 years)
- Change of muscle atrophy by quantitative lower extremity muscle MRI (10 years and older)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of forced expiratory volume in the first second (liter) (percentage predicted)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of peak expiratory flow (liter per second)(Change from baseline at 3 years and 5 years)
- Change of range of motion of elbows, wrist, hips, knee and ankle(Change from baseline at 3 years and 5 years)
- Change of location, level and characteristics of pain assessed by McGill pain questionnaire (12 years and older)(Change from baseline at 3 years and 5 years)
- Change of activity limitations assessed using ACTIVLIM (6 years and older)(Change from baseline at 3 years and 5 years)
- Change of bone density assessed using DEXA-scan (2 years and older)(Change from baseline at 3 years and 5 years)
- Change of functional ability in daily life assessed by Egen klassification scale version 2 (EK2) (16 years and older)(Change from baseline at 3 years and 5 years)
- Change of Functional Ambulation Category (FAC) (5 years and older)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of peak cough flow (liter per second)(Change from baseline at 3 years and 5 years)
- Change of muscle fattening (echo-intensity) assessed by muscle ultrasound(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of vital capacity (percentage predicted)(Change from baseline at 3 years and 5 years)
- Change of muscle fattening by quantitative lower extremity muscle MRI (10 years and older)(Change from baseline at 3 years and 5 years)
- Change of Graded and Timed function tests(Change from baseline at 3 years and 5 years)
- Change of muscle atrophy (cm) assessed by muscle ultrasound(Change from baseline at 3 years and 5 years)
- Change of muscle power assessed by muscle power measurements (Medical Research Council (MRC) scale) (2 years and older)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of forced vital capacity (percentage predicted)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of maximal inspiratory pressure (cmH2O)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of maximal expiratory pressure (cmH2O)(Change from baseline at 3 years and 5 years)
- Change of Quality of Life (pediatric; 2-17 years old) assessed by PedsQL neuromuscular module (NMM)(Change from baseline at 3 years and 5 years)
- Pulmonary function (5 years and older) - change of sniff nasal inspiratory pressure (cmH2O)(Change from baseline at 3 years and 5 years)
- Change of Quality of life (adult) assessed by SF36/RAND36(Change from baseline at 3 years and 5 years)
- Change of Quality of Life (adult) assessed by Individualized Neuromuscular Quality of Life (INQoL)(Change from baseline at 3 years and 5 years)
- Change of Brooke and Vignos scale (2 years and older)(Change from baseline at 3 years and 5 years)
- Change of Wong-Baker Faces Pain Scale (2 years and older)(Change from baseline at 3 years and 5 years)