Natural History Study for Patients With Nemaline Myopathy in Spain

NCT07488806 | Recruiting

• 1 other identifier: PR(AMI)251/2025
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Nemaline Myopathy; Myopathies; KLHL40; KLHL41; LMOD3; Cohort Studies; MYPN; TNNT3; Myopathic Conditions; NEB; ACTA1; TPM2; TPM3; TNNT1; CFL2; KBTBD13

Keywords

NATURAL HISTORY; NEMALINE MYOPATHY

Outcome Measures

Primary Outcomes (7)

• Observe changes in muscle echogenicity by muscle ultrasound.

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in motor function using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in motor function using the Hammersmith Infant Neurological Examination Section 2 (HINE-2)

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in Peabody Developmental Motor Scales (PDMS-3) Scale Score

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in motor function using the Motor Function Measure (MFM32) Scale Score

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in motor function using the North Star Ambulatory Assessment (NSAA) score

  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.

  Change from baseline through study completion, an average of 5 years

• Observe natural history changes in the Performance of Upper Limb (PUL) score

  Change in upper limb function assessed using the Performance of Upper Limb (PUL) scale. Higher scores indicate better function.

  Change from baseline through study completion, an average of 5 years

Secondary Outcomes (3)

• Observe the natural clinical progression in respiratory function.

  Change from baseline through study completion, an average of 5 years

• Observe changes in Nutritional Status

  Change from baseline through study completion, an average of 5 years

• Observe changes in Quality of Life

  Change from baseline through study completion, an average of 5 years

Study Arms (1)

All patients

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

Diagnostic Test: Muscle Ultrasound; Diagnostic Test: Motor function scales; Other: Complete physical examination; Other: Ventilatory/ respiratory, Cardiac and other support assessment; Other: QOL assessment, Neuropsychological; Device: Digital Biomarkers; Other: Oromotor function and nutrition; Other: Motor Milestone Assessments

Interventions

Muscle Ultrasound DIAGNOSTIC_TEST

Ultrasound guided evaluation of 28 muscles evaluated accross different body regions, assessed using the Heckmatt gradinf system (semiquantitative scale).

All patients

Motor function scales DIAGNOSTIC_TEST

Evaluation of patients motor function using motor scales (CHOP-INTEND, MFM32, HINE-2, NSAA, PDSM-3, RFF, 10m walk, PUL)

All patients

Complete physical examination OTHER

Complete physical evaluations including muscle power and goniometry measurements

All patients

Digital Biomarkers DEVICE

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.

All patients

Ventilatory/ respiratory, Cardiac and other support assessment OTHER

Assessment of ventilatory, cardiac, nutritional, and other support needs

All patients

QOL assessment, Neuropsychological OTHER

Assessment of quality of life

All patients

Oromotor function and nutrition OTHER

Assessment of bulbar funcionality: feeding devices, nutritional status.

All patients

Motor Milestone Assessments OTHER

Motor milestones age of acquisition and loss (if applicable)

All patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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).

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Study Sites (1)

University Hospital Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Myopathies, Nemaline; Muscular Diseases

Interventions

Respiratory Rate; Nutritional Status

Condition Hierarchy (Ancestors)

Myopathies, Structural, Congenital; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Health Status; Demography; Population Characteristics

Central Study Contacts

Laura Costa-Comellas, M.D.

CONTACT

+34677255332; laura.costacomellas@vallhebron.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 23, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2032
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

ES (1)