Natural History Study of Children With LAMA2-related Dystrophies

NCT ID: NCT06354790

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-12-05

Study Completion Date

2027-12-31

Brief Summary

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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

Detailed Description

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The international workshop on LAMA2-RD, held in 2019 in Maastricht, stressed the importance of the identification of LAMA2-RD patients and the natural history studies worldwide. Together with the recent progress in preclinical applications, the road to therapy is paved.

However, no effective treatment has currently received market approval. Given the phenotype variability in LAMA2-RD patients, even in very young ones, determining which outcome measure(s) could be the most appropriate to assess the efficacy of potential therapies, and which variables are prognostic of the disease course, is required. In consequence, it is clearly necessary to explore all the aspects of the pathology: physiological, clinical/motor, biological, aligning with current or future international studies though collaboration.

Unlike results obtained through a retrospective study, data from a prospective natural history will be less subject to bias and error. Control of the studied population will also lead to reduce the variability of the results. The different variables explored during this study aim to cover all aspects of the disease and appear to be relevant candidates as outcomes.

The aim of the study is to focus on the clinical phenotyping and to establish a well-described cohort of patients in France with LAMA2-RD for prospective follow-up and recruitment for future clinical trials. One other objective is to validate the use of a large subset of outcome measures in LAMA2-RD. Adding an electrophysiological data will give more insight to the neuropathology of the disease and enlarge the scope of futures therapies.

An exploratory part will test if denaturation profiling of plasma from patients can be used to follow disease progression. Finally, serum and plasma samples from patients will also be stored for future studies focused on searching and validating novel biomarkers in LAMA2-RD.

Conditions

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Merosin Deficient Congenital Muscular Dystrophy

Keywords

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LAMA2 Congenital Muscular Dystrophy Natural history

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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All patients

Motor evaluations

Intervention Type 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)

Cognitive assessment

Intervention Type OTHER

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

Pulmonary function test

Intervention Type OTHER

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

Cardiac evaluation

Intervention Type OTHER

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

Quality of life

Intervention Type OTHER

Evaluation of patients quality of life with questionnaires and PROM

Spine X Ray

Intervention Type OTHER

Evaluation of spinal deformities by X-ray

Muscular MRI

Intervention Type OTHER

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

Biomarkers collection and analysis

Intervention Type OTHER

Collection of blood and urinary sample for biomarkers research.

Interventions

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Motor evaluations

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)

Intervention Type OTHER

Cognitive assessment

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

Intervention Type OTHER

Pulmonary function test

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

Intervention Type OTHER

Cardiac evaluation

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

Intervention Type OTHER

Quality of life

Evaluation of patients quality of life with questionnaires and PROM

Intervention Type OTHER

Spine X Ray

Evaluation of spinal deformities by X-ray

Intervention Type OTHER

Muscular MRI

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

Intervention Type OTHER

Biomarkers collection and analysis

Collection of blood and urinary sample for biomarkers research.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

2 Years

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Association Française contre les Myopathies (AFM), Paris

OTHER

Sponsor Role collaborator

Institut de Myologie, France

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Centre de Référence GNMH, Pédiatrie Hôpital Raymond-Poincaré

Garches, , France

Site Status NOT_YET_RECRUITING

Service de MPR pédiatrique L'Escale - HCL

Lyon, , France

Site Status NOT_YET_RECRUITING

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

Montpellier, , France

Site Status NOT_YET_RECRUITING

Plateforme d'essais cliniques pédiatriques iMotion

Paris, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Andreea SEFERIAN, Dr

Role: CONTACT

Phone: +33 (0)1 71 73 80 50

Email: [email protected]

Erwan GASNIER, PhD

Role: CONTACT

Facility Contacts

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Isabelle BOSSARD

Role: primary

Manel SAIDI

Role: primary

Léa THEVENET

Role: primary

Dominique DUCHENE

Role: primary

Other Identifiers

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NatHis LAMA2

Identifier Type: -

Identifier Source: org_study_id