NCT07201636

Natural History Study for Patients With Nemaline Myopathy in Belgium

A Monocentre, Prospective, Longitudinal and Observational Natural History Study for Patients With Nemaline Myopathy

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: Centre Hospitalier Universitaire de Liege · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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: Medical and neurological examinations Age- and ability-adapted motor and respiratory outcome measures Questionnaires assessing swallowing, fatigue, quality of life, and health economics. Visit durations will vary based on age and ability, including standard care appointments. This study will provide critical longitudinal data to support the development of future clinical trials by identifying relevant outcome measures and potential biomarkers for NM.

Conditions

• Nemaline Myopathy

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Motor Function Assessments	The planned functional motor assessments are specific to age and degree of motor impairment. Participants are expected to have varying degrees of motor impairment, for example some will be non-ambulant. There is also a wide range of ages of participants. Therefore, some assessments will not be applicable. Some participants may gain or lose these abilities during the study and the assessments they complete shall be tailored accordingly aiming to reflect their most typical abilities on the day assessed.
DEVICE	Syde	Syde is an innovative device intended to be used in a home-based environment. It is composed of two watch-like sensors, each containing a magneto-inertial sensors that record the linear acceleration, the angular velocity, the magnetic field of the movement in all directions.The two watches can be worn as wristwatch or placed near the ankle.
DIAGNOSTIC_TEST	Respiratory Assessments	The planned respiratory assessments are tailored to the participant's age and respiratory capacity. Participants are expected to have varying degrees of respiratory impairment, and some assessments may not be applicable to all. As participants may gain or lose respiratory function over the course of the study, the assessments completed will be adapted accordingly to reflect their most typical respiratory abilities on the day of assessment.
DIAGNOSTIC_TEST	Bulbar Function Questionnaires	The planned bulbar function assessments are age-specific and designed to reflect the participant's typical oral intake abilities. For participants aged 1-17 years, the Children's Eating and Drinking Activity Scale (CEDAS), will be used. For those aged 18 years and older, the Functional Oral Intake Scale (FOIS) will be applied. Both tools are part of a unified 7-item scale validated across paediatric and adult populations, ensuring continuity across age groups.
DIAGNOSTIC_TEST	Clinical Global Impression (CGI)	The Clinical Global Impression (CGI) tool will be used to assess overall disease severity and improvement across three functional domains: Physical Motor Function, Respiratory Function, and Bulbar Function. Assessments are based on clinician judgment using all available clinical data and are conducted by clinicians experienced with the disease under study.
OTHER	Quality of Life Questionnaires	The planned quality of life and functional status assessments are designed to capture the participant's overall well-being and daily functioning, taking into account the wide range of ages and disease severities in the study population. Validated questionnaires appropriate to age and functional level will be used to evaluate aspects such as health-related quality of life, fatigue, and daily activity limitations.
PROCEDURE	Blood Sample Collection	Blood sample collection is usually done annually for NM patients as part of their standard of care. This is usually done by a nurse or a medical doctor according to standard guidelines for blood sampling. During routine blood sampling, additional blood will be collected and up to 20 ml of blood will be taken.

Timeline

• Start date: 2026-08-01
• Primary completion: 2029-04-01
• Completion: 2029-08-01
• First posted: 2025-10-01
• Last updated: 2026-03-25

Locations

1 site across 1 country: Belgium