Trial Readiness and Trial Fitness for Congenital Myopathies: a 2-year Prospective Natural History Study Including a Cross-sectional Study on Muscle Fatigability
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change of Motor Function Measure (MFM)
研究概览
简要总结
Core myopathies (CCD/MmD), nemaline myopathies (NEM) and centronuclear myopathies (CNM) are three types of rare congenital myopathies. Not much is known about the natural history and no curative treatment is available for these groups. Also patients report fatigability as one of their symptoms. The goal of this observational study is to study the natural history during 24 months to achieve trial readiness and to study the muscle fatigability in CCD/MmD, NEM and CNM.
详细描述
Rationale: Patients with CCD/MmD, NEM and CNM report symptoms of weakness in the arms and legs. Other symptoms include weakness of the respiratory, facial and swallowing muscles. No treatments are available for congenital myopathies (CM) to slow down or cure the disease. A few type I-II trials have taken place and more are expected. Therefore it is important to reach trial readiness. To create trial readiness, there is a need for natural history study to create a detailed report of the disease course and a selection of the most sensitive clinical and functional outcome measures and biomarkers. Besides muscle weakness, several patients report muscle fatigability. This has not been investigated systematically in CM. The lack of evidence calls for a cross-sectional study assessing muscle fatigability and neuromuscular transmission in CM.
Objectives: i) To assess the natural disease course of CCD/MmD, NEM and CNM during 24 months. ii) To select relevant and sensitive clinical and functional outcome measures and biomarkers. iii) To assess the severity of muscle fatigability in CCD/MmD, NEM and CNM.
Study design: Patients with a genetically confirmed CCD/MmD, NEM or CNM will be able to participate in this study. The study consist of 2 parts. Part 1: a prospective cohort study with 5 visits every 6 months, for a total of 2 years. 45 patients will be included for this part. Part 2: an observational study with 2 visits. For this part 75 patients will be included. There will be an overlap in patients for the two parts. So a total of approximately 100 patients will be included. A large set of tests will be performed to assess the full capabilities of the patient, e.g. muscle strength/endurance, muscle imaging (MRI/ultrasound), activities, walking ability, quality of life, muscle fatigability and the feeling of fatigue.
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Change of Motor Function Measure (MFM)
时间窗: Change from baseline at 6, 12, 18 and 24 months
Global motor functioning. The main outcome is the change in MFM score over a period of 2 years. The scores of the patients will also be compared to reference values.
Endurance shuttle test - fatigability part
时间窗: At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.
Patients walk/move blocks/move pegs at a personalised set speed. The main outcome is if the patient drops out due to the speed being too low. If the patient drops out the time until dropout is noted.
次要结局
- Vitamin D3(At baseline)
- Change of graded and timed rise from floor (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Change of bone density (DEXA scan) (6 years and older)(Change from baseline at 24 months)
- Accelerometry - change of extent and intensity of physical activity in daily life (all ages)(Change from baseline at 6, 12, 18 and 24 months)
- Change of 6-minute walk test (6MWT) (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Change of muscle atrophy by quantitative lower extremity muscle MRI (10 years and older)(Change from baseline at 24 months)
- Range of motion (all ages)(Change from baseline at 6, 12, 18 and 24 months)
- Pulmonary function - change of forced vital capacity (percentage predicted) (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Pulmonary function - change of maximal inspiratory pressure (cmH2O) (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Vignos and Brooke scale (all ages)(Change from baseline at 6, 12, 18 and 24 months)
- Liver function panel(At baseline)
- Change in muscle fattening (echo-intensity) assessed by muscle ultrasound (all ages)(Change from baseline at 24 months)
- Repetitive nerve stimulation (RNS) (8-60 years old) - fatigability part(At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.)
- Fatigue severity scale questionnaire (12 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- PROMIS Fatigue Short Form questionnaire (all ages)(Change from baseline at 6, 12, 18 and 24 months)
- McGill pain questionnaire (MPQ) (12 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- PedsQL generic quality of life (2-17 years old)(Change from baseline at 6, 12, 18 and 24 months)
- Short Form 36 (SF36) quality of life scale (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Impact on participation and autonomy (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Handheld dynamometry (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Creatine Kinase(At baseline)
- Calcium(At baseline)
- Pulmonary function - change of maximal expiratory pressure (cmH2O) (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Checklist individual strength (CIS) questionnaire fatigue subscale (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Borg rating scale of perceived exertion (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Hospital anxiety and depression scale (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- PedsQL neuromuscular module (NMM) (2-17 years old)(Change from baseline at 6, 12, 18 and 24 months)
- Effects of pyridostigmine and/or salbutamol (8-60 years old) - fatigability part(At baseline of the fatigability part of the study)
- Manual muscle testing (MMT) (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Change in muscle fattening by quantitative lower extremity muscle MRI (10 years and older)(Change from baseline at 24 months)
- Pulmonary function - change of forced expiratory volume in the first second (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Pulmonary function - change of sniff nasal inspiratory pressure (5 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Isokinetic dynamometry (quadriceps and hamstrings or biceps and triceps) (8-60 years old) - fatigability part(At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.)
- Wong-Baker Faces Pain Scale (2-11 years old)(Change from baseline at 6, 12, 18 and 24 months)
- Resilience evaluation scale (18 years and older)(Change from baseline at 6, 12, 18 and 24 months)
- Change in muscle atrophy (cm) assessed by muscle ultrasound (all ages)(Change from baseline at 24 months)
- Change in surface electromyography (EMG) amplitude and median frequency during isokinetic dynamometry with surface EMG (quadriceps and hamstrings or biceps and triceps) (8-60 years old) - fatigability part(At assessment 1 or 2 of the fatigability part of the study. Which day is dependent on the preference of the patient and planning possibilities.)
- PedsQL multidimensional fatigue scale (MFS) (2-17 years old)(Change from baseline at 6, 12, 18 and 24 months)
- Activlim questionnaire (7-17 years old)(Change from baseline at 6, 12, 18 and 24 months)