Natural History Study for Patients With Nemaline Myopathy in Belgium

Official title

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

Overview

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.

Interventions

• 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 ass
• 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.

Primary outcome measures

• Change in Motor Function Measure (MFM32) Score [Time frame: Over 3 years]
• Change in Ventilation Hours per Day [Time frame: Over 3 years]

Secondary outcome measures (2)

• Change in Quality of Life Score (PROMIS-29 Profile v2.1) [Time frame: Over 3 years]
• Drop-out Rate [Time frame: Over 3 years]

Eligibility criteria

Inclusion criteria

• Male or Female
• Any age
• 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.

Exclusion criteria

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Belgium · 1 center

• Centre de référence des maladies neuromusculaire, Centre Hospitalier Régional de la Citade — Liège

Identifiers

NCT: NCT07201636 · Acti-Nemaline

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗