ACTA1, CFL2, Cohort Studies, KBTBD13, KLHL40, KLHL41, LMOD3, Myopathic Conditions, Myopathies, MYPN, NEB, Nemaline Myopathy, TNNT1, TNNT3, TPM2, TPM3
Conditions
Keywords
NATURAL HISTORY, NEMALINE MYOPATHY
Brief summary
The objective of this natural history study is to comprehensively characterize the disease progression and clinical features of nemaline myopathies. The study aims to establish a well-defined cohort of patients in Spain, enabling long-term follow-up and facilitating recruitment for future clinical trials.
Detailed description
The aims of the study are: * Identify the specific genes and mutations responsible for NM in Spain. * Define the in-depth phenotyping of NM and the phenotype-genotype relationship. * Characterize the natural history of NM through the systematic collection of clinical (retrospective and prospective data), functional, and respiratory data in diagnosed patients in order to: * Describe the progression of the disease without disease-modifying therapies. * Identify reliable biomarkers and outcome measures for future clinical trials. * Align the national protocol with international efforts to generate comparable data.
Interventions
DIAGNOSTIC_TESTMuscle Ultrasound
Ultrasound guided evaluation of 28 muscles evaluated accross different body regions, assessed using the Heckmatt gradinf system (semiquantitative scale).
DIAGNOSTIC_TESTMotor function scales
Evaluation of patients motor function using motor scales (CHOP-INTEND, MFM32, HINE-2, NSAA, PDSM-3, RFF, 10m walk, PUL)
Complete physical evaluations including muscle power and goniometry measurements
OTHERVentilatory/ respiratory, Cardiac and other support assessment
Assessment of ventilatory, cardiac, nutritional, and other support needs
Assessment of quality of life
DEVICEDigital Biomarkers
Video/photos with the aim is to record actions such as lifting a glass, raising arms above the head, getting up from the floor or a chair, walking, or running, in order to later analyze in detail how these movements are performed.
Assessment of bulbar funcionality: feeding devices, nutritional status.
Motor milestones age of acquisition and loss (if applicable)
Sponsors
Hospital Universitari Vall d'Hebron Research Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with a confirmed clinical and genetic diagnosis of MN (mutations in ACTA1, NEB, TPM2, TPM3, KBTBD13, CFL2, KLHL40, KLHL41, LMOD3, MYPN, TNNT1, TNNT3), or under discussion if they only have a compatible biopsy. * Signed informed consent by the patient or Legal Authority Responsible, and/or assent by the subject (in pediatric population).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observe changes in muscle echogenicity by muscle ultrasound. | Change from baseline through study completion, an average of 5 years | A standardized muscle ultrasound protocol of assessment is performed (whole body). Muscle images are scored using the Heckmatt scale (score 1-4): * Heckmatt grade 1 represents a normal muscle image. * Heckmatt grade 2 shows an increased echogenicity without attenuation of the deeper image regions. * Heckmatt grade 3 indicates a larger increase in echogenicity with some visible loss of normal muscle architecture. * Heckmatt grade 4 shows a strongly increased echogenicity with complete loss of recognizable muscle architecture. |
| Observe natural history changes in motor function using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) | Change from baseline through study completion, an average of 5 years | The CHOP-INTEND assesses a child's ability to move their body in a lying down position, supported sitting, and assisted rolling through 16 items. Scores range from 0 to 64, with higher scores indicating better motor function. Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. |
| Observe natural history changes in motor function using the Hammersmith Infant Neurological Examination Section 2 (HINE-2) | Change from baseline through study completion, an average of 5 years | This is a 37-item measure of infant developmental motor milestones that will be performed in participants aged 0-24months. Scores are interpreted in relation to optimality scores and cut-off scores for the participant's age. Higher scores represented higher function. |
| Observe natural history changes in Peabody Developmental Motor Scales (PDMS-3) Scale Score | Change from baseline through study completion, an average of 5 years | Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. PDMS-3 measures various motor abilities in young children. Four types of normative scores are yielded: age equivalents, percentile ranks, subtest scaled scores, and composite index scores. Higher scores indicate higher level of function. |
| Observe natural history changes in motor function using the Motor Function Measure (MFM32) Scale Score | Change from baseline through study completion, an average of 5 years | Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. This motor function assessment consists of 32 items organized in three dimensions: standing position and transfers, axial and limb proximal motor function, and limb distal motor function. Total scores are given between 0-100, with 0 indicating severe functional impairment and 100 indicating no functional impairment. |
| Observe natural history changes in motor function using the North Star Ambulatory Assessment (NSAA) score | Change from baseline through study completion, an average of 5 years | Change in motor function assessed using age-appropriate validated motor scales and dependent on patient's ability. Scores in the NSAA scale range from 0 to 34, with higher scores indicating better motor function. |
| Observe natural history changes in the Performance of Upper Limb (PUL) score | Change from baseline through study completion, an average of 5 years | Change in upper limb function assessed using the Performance of Upper Limb (PUL) scale. Higher scores indicate better function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observe the natural clinical progression in respiratory function. | Change from baseline through study completion, an average of 5 years | Respiratory function will be assessed longitudinally using age-appropriate measures depending on patient ability. Respiratory status will include ventilatory support requirements (none, non-invasive ventilation, or invasive ventilation) and time on/off ventilator, when feasible. Forced vital capacity (FVC), expressed as percent predicted for age and sex, will be used when spirometry is possible. |
| Observe changes in Nutritional Status | Change from baseline through study completion, an average of 5 years | Assessment of nutritional status over time through indicators such as feeding method (oral versus enteral feeding) and need for nutritional support. Swallowing status and dietary modifications will be recorded when applicable. Changes from baseline will be analyzed to evaluate nutritional progression and feeding outcomes. |
| Observe changes in Quality of Life | Change from baseline through study completion, an average of 5 years | Assessment of patient or caregiver-reported quality of life using validated questionnaires appropriate for age and functional status, including standardized health-related quality of life instruments (the Clinical Global Impression-Severity \[CGI-S\], the Clinical Global Impression-Change \[CGI-C\], Patient Global Impression of Change \[PGI-C\], and Patient Global Impression of Severity \[PGI-S\]). Total scores and domain-specific scores will be analyzed. Changes from baseline will be evaluated to assess perceived health status and daily functioning. |
Countries
Spain
Contacts
CONTACTLaura Costa-Comellas, M.D.
Outcome results
None listed