Natural History Study of Children With LAMA2-related Dystrophies

Merosin Deficient Congenital Muscular Dystrophy Clinical Trial

— LAMA2  

Official title:

A Prospective, Longitudinal, Interventional Natural History Study of Children With LAMA2-related Dystrophies

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06354790
• Other study ID #: NatHis LAMA2
• Status: Not yet recruiting
• Start date: June 15, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: Institut de Myologie, France
• Contact: Andreea SEFERIAN, Dr
• Phone: +33 (0)1 71 73 80 50
• Email: a.seferian[@]institut-myologie.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 31, 2027
• Est. primary completion date: June 14, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 15 Years

Eligibility

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

Related Conditions & MeSH terms

• Merosin Deficient Congenital Muscular Dystrophy
• Muscular Dystrophies

Intervention

Other:
• 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)
• Cognitive assessment
Patients cognitive evaluation (WPPSI-IV, WISC-V)
• Pulmonary function test
Evaluation of patients' respiratory function (FVC, PCF, MIP, MEP, SNIP)
• Cardiac evaluation
Evaluation of patients' cardiac function (ECG, Echo-cardiography)
• Quality of life
Evaluation of patients quality of life with questionnaires and PROM
• Spine X Ray
Evaluation of spinal deformities by X-ray
• Muscular MRI
Evaluation of a qualitative whole-body muscle part and a quantitative lower limb muscle part by MRI
• Biomarkers collection and analysis
Collection of blood and urinary sample for biomarkers research.

Locations

Country	Name	City	State
France	Centre de Référence GNMH, Pédiatrie Hôpital Raymond-Poincaré	Garches
France	Service de MPR pédiatrique L'Escale - HCL	Lyon
France	Département de neuropédiatrie Pôle Femme Mère Enfant CHU de Montpellier - Hôpital Gui de Chauliac	Montpellier
France	Plateforme d'essais cliniques pédiatriques iMotion	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Myologie, France	Association Française contre les Myopathies (AFM), Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Motor function Measurement (MFM32) score		Through study completion, an average of 2 years
Primary	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
Primary	Change in Revised Upper Limb Module (RULM) score		Through study completion, an average of 2 years
Primary	Change in grip strength measured by dynamometer tool		Through study completion, an average of 2 years
Primary	Change in pinch strength measured by dynamometer tool		Through study completion, an average of 2 years
Primary	Change in arm flexion/extension strength measured by dynamometer tool		Through study completion, an average of 2 years
Primary	Change in 6 Minutes Walking Test		Through study completion, an average of 2 years
Primary	Change in 4 Stairs Climbing Test (4SCT)		Through study completion, an average of 2 years
Primary	Change in 10m Walking Test		Through study completion, an average of 2 years
Primary	Change in Rise from Floor Test		Through study completion, an average of 2 years
Primary	Change in patient's Forced Vital Capacity (FVC) results		Through study completion, an average of 2 years
Primary	Change in patient's Peak Cough Flow (PCF) results		Through study completion, an average of 2 years
Primary	Change in patient's Maximum Expiratory Pressure (MEP) results		Through study completion, an average of 2 years
Primary	Change in patient's Maximal Inspiratory Pressure (MIP) results		Through study completion, an average of 2 years
Primary	Change in patient's Sniff Nasal Inspiratory Pressure (SNIP) results		Through study completion, an average of 2 years
Primary	Change in patient's muscle fat replacement measured by Magnetic Nuclear Resonance		Through study completion, an average of 2 years
Primary	Change in patient's cross-sectional area of the residual muscle measured by MNR		Through study completion, an average of 2 years
Secondary	Change in Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV) results		Through study completion, an average of 2 years
Secondary	Change in Wechsler Intelligence Scale for Children-V (WISC-V) results		Through study completion, an average of 2 years
Secondary	Change in PedsQL questionnaire results		Through study completion, an average of 2 years
Secondary	Change in CGI-S questionnaire results		Through study completion, an average of 2 years
Secondary	Change in CGI-I questionnaire results		Through study completion, an average of 2 years
Secondary	Change in Faces pain rating scale results		Through study completion, an average of 2 years
Secondary	Change in Fatigue Severity Scale results		Through study completion, an average of 2 years
Secondary	Change in ACTIVLIM questionnaire results		Through study completion, an average of 2 years
Secondary	Change in Egen Klassifikation Scale Version 2 (EK2) results		Through study completion, an average of 2 years
Secondary	Change in Caregiver burden questionnaire (LMDIS) results	LAMA2 Dystrophy Independence Scale	Through study completion, an average of 2 years