Natural History Study of Children With LAMA2-related Dystrophies

NCT06354790 | Recruiting

• 1 other identifier: NatHis LAMA2
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this natural history study is to characterize the disease course, characteristics in paediatric population of LAMA2-RD (related dystrophies) patients. The aim of the study is to establish a well-described cohort of patients in France with LAMA2-RD for prospective follow-up and recruitment for future clinical trials. Participants will be follow up during a two years period regarding exhaustive aspects of the pathology:

• Muscular function
• Respiratory function
• Cognitive phenotyping
• Quality of life
• Growth parameters
• Biomarkers

Conditions

Merosin Deficient Congenital Muscular Dystrophy

Keywords

LAMA2; Congenital Muscular Dystrophy; Natural history

Outcome Measures

Primary Outcomes (17)

• Change in Motor function Measurement (MFM32) score

  Through study completion, an average of 2 years

• Change in Motor Milestone Checklist

  Acquisitions and losses of motor functions (ex: Head control, sitting, crawling, standing, walking, climbing stairs, jumping,running, hopping,...)

  Through study completion, an average of 2 years

• Change in Revised Upper Limb Module (RULM) score

  Through study completion, an average of 2 years

• Change in grip strength measured by dynamometer tool

  Through study completion, an average of 2 years

• Change in pinch strength measured by dynamometer tool

  Through study completion, an average of 2 years

• Change in arm flexion/extension strength measured by dynamometer tool

  Through study completion, an average of 2 years

• Change in 6 Minutes Walking Test

  Through study completion, an average of 2 years

• Change in 4 Stairs Climbing Test (4SCT)

  Through study completion, an average of 2 years

• Change in 10m Walking Test

  Through study completion, an average of 2 years

• Change in Rise from Floor Test

  Through study completion, an average of 2 years

• Change in patient's Forced Vital Capacity (FVC) results

  Through study completion, an average of 2 years

• Change in patient's Peak Cough Flow (PCF) results

  Through study completion, an average of 2 years

• Change in patient's Maximum Expiratory Pressure (MEP) results

  Through study completion, an average of 2 years

• Change in patient's Maximal Inspiratory Pressure (MIP) results

  Through study completion, an average of 2 years

• Change in patient's Sniff Nasal Inspiratory Pressure (SNIP) results

  Through study completion, an average of 2 years

• Change in patient's muscle fat replacement measured by Magnetic Nuclear Resonance

  Through study completion, an average of 2 years

• Change in patient's cross-sectional area of the residual muscle measured by MNR

  Through study completion, an average of 2 years

Secondary Outcomes (10)

• Change in Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV) results

  Through study completion, an average of 2 years

• Change in Wechsler Intelligence Scale for Children-V (WISC-V) results

  Through study completion, an average of 2 years

• Change in PedsQL questionnaire results

  Through study completion, an average of 2 years

• Change in CGI-S questionnaire results

  Through study completion, an average of 2 years

• Change in CGI-I questionnaire results

  Through study completion, an average of 2 years

Study Arms (1)

All patients

Other: Motor evaluations; Other: Cognitive assessment; Other: Pulmonary function test; Other: Cardiac evaluation; Other: Quality of life; Other: Spine X Ray; Other: Muscular MRI; Other: Biomarkers collection and analysis

Interventions

Motor evaluations OTHER

Evaluation of patients motor function using motor scales (MFM32, RULM), Timed functioned tests (6MWT, Rise from floor, 4SCT, 10mWT), dynamometric strength evaluation (grip, pinch, flexion/extension)

All patients

Cognitive assessment OTHER

Patients cognitive evaluation (WPPSI-IV, WISC-V)

All patients

Pulmonary function test OTHER

Evaluation of patients' respiratory function (FVC, PCF, MIP, MEP, SNIP)

All patients

Cardiac evaluation OTHER

Evaluation of patients' cardiac function (ECG, Echo-cardiography)

All patients

Quality of life OTHER

Evaluation of patients quality of life with questionnaires and PROM

All patients

Spine X Ray OTHER

Evaluation of spinal deformities by X-ray

All patients

Muscular MRI OTHER

Evaluation of a qualitative whole-body muscle part and a quantitative lower limb muscle part by MRI

All patients

Biomarkers collection and analysis OTHER

Collection of blood and urinary sample for biomarkers research.

All patients

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

40 young patients aged between 2 and 15 years old (inclusive) at time of consent, with a confirmed LAMA2 diagnosis (muscle biopsy with absence of merosin (laminin-211) and at least one pathogenic variant in the LAMA2 gene)

You may qualify if:

• Signed informed consent by the Legal Authority Responsible and/or assent by the subject (starting from 6 years old)
• Subject must be
• Supportive clinical phenotype and diagnosis of LAMA2-RD, confirmed by:
• Two pathogenic variants in the LAMA2 gene (via a diagnostic laboratory included on an approved list of genetic testing laboratories (Annex 1)) or
• Muscle biopsy with absence of merosin (laminin-211) and at least one pathogenic variant in the LAMA2 gene
• Absence of another confirmed neurological genetic disease
• Willingness to maintain current exercise and/or physical therapy regimen for the duration of the clinical study
• Willingness to comply with the study protocol, including all the mandatory study procedures and visits
• Affiliated to or a beneficiary of a French or acknowledged in France, social security scheme

You may not qualify if:

• Developmental quotient less than 70 and/or behavioral disorder requiring general anesthesia to perform an MRI
• Acute medical illness or hospitalization within 30 days prior to informed consent
• Participation in a previous trial of any investigational agent for LAMA2-RD, or use of any other investigational therapy within 30 days prior to informed consent, or participation in other clinical studies, within 30 days (or 5 half-lives, whichever is longer) prior to informed consent, which, in the opinion of the PI, may potentially confound results from this study
• Other significant medical condition and/or overall fragility of medical status, which in the opinion of the Investigator may confound interpretation of the clinical course of LAMA2-RD
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Institut de Myologie, France: lead
• Association Française contre les Myopathies (AFM), Paris: collaborator

Study Sites (4)

Centre de Référence GNMH, Pédiatrie Hôpital Raymond-Poincaré

Garches, France

NOT YET RECRUITING

Service de MPR pédiatrique L'Escale - HCL

Lyon, France

NOT YET RECRUITING

Département de neuropédiatrie Pôle Femme Mère Enfant CHU de Montpellier - Hôpital Gui de Chauliac

Montpellier, France

NOT YET RECRUITING

Plateforme d'essais cliniques pédiatriques iMotion

Paris, France

RECRUITING

MeSH Terms

Conditions

Muscular dystrophy congenital, merosin negative

Interventions

Mental Status and Dementia Tests; Respiratory Physiological Phenomena; Quality of Life

Intervention Hierarchy (Ancestors)

Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities; Circulatory and Respiratory Physiological Phenomena; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health

Central Study Contacts

Andreea SEFERIAN, Dr

CONTACT

+33 (0)1 71 73 80 50; a.seferian@institut-myologie.org

Erwan GASNIER, PhD

CONTACT

Study Design

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

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 9, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): December 4, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)