The Natural History and Muscle Fatigability of Patients With Congenital Myopathies.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Natural history and non therapeutical therapy.
- Who it may be relevant to
- Registry conditions: Central Core Disease, Multi-Minicore Disease, Nemaline Myopathy, Centronuclear Myopathy. Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Trial Readiness and Trial Fitness for Congenital Myopathies: a 2-year Prospective Natural History Study Including a Cross-sectional Study on Muscle Fatigability
Overview
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.
Detailed description
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.
Interventions
- Other Natural history and non therapeutical therapy
This study concerns a natural history study part and a muscle fatigability part. For the natural history study no interventions will be used. For the muscle fatigability part non therapeutical therapies will be used. This includes endurance tests, isokinetic dynamometry and repetitive nerve stimulation.
Primary outcome measures
- Change of Motor Function Measure (MFM) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Endurance shuttle test - fatigability part [Time frame: 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.]
Secondary outcome measures (12)
- Change of 6-minute walk test (6MWT) (5 years and older) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Accelerometry - change of extent and intensity of physical activity in daily life (all ages) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Change of bone density (DEXA scan) (6 years and older) [Time frame: Change from baseline at 24 months]
- Change of graded and timed rise from floor (5 years and older) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Handheld dynamometry (5 years and older) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Creatine Kinase [Time frame: At baseline]
- Vitamin D3 [Time frame: At baseline]
- Calcium [Time frame: At baseline]
- Liver function panel [Time frame: At baseline]
- Manual muscle testing (MMT) (5 years and older) [Time frame: Change from baseline at 6, 12, 18 and 24 months]
- Change in muscle fattening by quantitative lower extremity muscle MRI (10 years and older) [Time frame: Change from baseline at 24 months]
- Change of muscle atrophy by quantitative lower extremity muscle MRI (10 years and older) [Time frame: Change from baseline at 24 months]
Eligibility criteria
Inclusion Criteria for the natural history:
- 2 years or older
- Willing and able to complete the measurement protocol
- Willing and able to travel to Nijmegen and Utrecht
- Dutch-speaking
- Genetically-confirmed congenital myopathy (CCD/MmD, NEM, and CNM)
Inclusion Criteria for the fatigability study:
- 8-60 years old
- Willing and able to complete the measurement protocol
- Willing and able to travel to Nijmegen and Utrecht
- Dutch-speaking
- Genetically-confirmed congenital myopathy (CCD/MmD, NEM, and CNM)
- Willing to stop taking pyridostigmine and/or salbutamol 24 hours before the visit.
Exclusion Criteria for both parts:
Other neuromuscular, psychiatric or neurological disorders.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Netherlands · 2 centers
- Radboudumc — Nijmegen
- UMC Utrecht — Utrecht
Publications
- van de Camp SAJH, Brenninkmeijer R, van Doorn JLM, de Laat ECM, Pomp L, Stinissen L, Cameron D, Groothuis JT, van Alfen N, Jungbluth H, Erasmus CE, Bartels B, Wadman RI, Voet NBM, van der Pol WL, Voermans NC. READYCOM: protocol for a 2-year prospective natural history and cross-sectional muscle-fatigability study for improving trial readiness in congenital myopathies. BMJ Open. 2026 Aug 4;16(8):e1 PMID 42551994
Identifiers
NCT: NCT06157268 · NL83069.000.23 · W.OR22-10