Prospective Study of the Natural History of Patients With Type 2 and 3 Spinal Muscular Atrophy

Study Overview
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Brief Summary
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NatHis-SMA is a prospective, longitudinal and interventional study of the natural history of patients with type 2 and 3 Spinal Muscular Atrophy (SMA). The purpose of this study is to characterize the disease course over 2 years and identify prognostic variables of the disease and biomarkers of SMA progression, as well as determine the best outcome measures for further therapeutics approaches.

Official Title
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Prospective Study of the Natural History of Patients With Type 2 and 3 Spinal Muscular Atrophy

Conditions
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Type 2 Spinal Muscular Atrophy, Type 3 Spinal Muscular Atrophy

Intervention / Treatment
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* Other: Strength, function and activity measurements
* Other: Muscle MRI
* Other: Electrophysiology measurements
* Other: Blood sampling for biomarker analysis


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Type 2 or 3 spinal muscular atrophy genetically confirmed Age superior or equal to 2 years old up to 30 years of age included For patients older than 6 years old, willing and able to comply with all protocol requirements and procedures. For non-ambulant patients, able to sit upright in a wheelchair for at least three hours Patients over 18 years of age and parent(s)/legal guardian(s) of patients < 18 years of age must provide written informed consent prior to participating in the study and informed assent will be obtained from minors at least 7 years of age when required by regulation. In France only: Affiliated to or a beneficiary of a social security category EXCLUSION CRITERIA Previously treated with an investigational drug within 6 months prior the recruitment in this study. Other condition which may significantly interfere with the assessment of the SMA and is clearly not related to the disease Current or anticipated participation in any therapeutic investigational clinical studies. Patients with specific contraindication to MRI (i.e. metallic foreign body, claustrophobia, and others deemed to be prohibitive by the investigators) will be allowed to participate, but MRI will not be performed. For women : pregnancy or current breastfeeding

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Strength, function and activity measurements|nan|
|Other: Muscle MRI|nan|
|Other: Electrophysiology measurements|nan|
|Other: Blood sampling for biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of muscle strength | Study-specific assessments: Grip and pinch strength | Baseline and then every 6 months until end of the study, up to 24 months | 
| Change from baseline of motor function | Study-specific assessments: Moviplate and MFM scores, upper extremity functional reaching volume, timed tests (time to rise from floor, time to walk 10 meters, time to climb and descend stairs, distance walked on the Six-Minute Walk Test) | Baseline and then every 6 months until end of the study, up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of respiratory function | Study-specific assessments: Pulmonary function tests | Baseline and then every 6 months until end of the study, up to 24 months | 
| Change from baseline of physical activity of upper limbs movements | Quantity and duration of movements, time of inactivity during the day | Baseline and then every 6 months until end of the study, up to 24 months | 
| Change from baseline of skeletal muscle nuclear magnetic resonance (NMR) imaging (MRI) | Muscle volume changes, intramuscular fatty infiltration progression, indices of disease activity (only for Paris and Strasbourg sites and for patients older than 4 years) | Baseline and then every 12 months until the end of the study, up to 24 months | 
| Change from baseline of electrophysiology measurements | Compound Motor Action Potential (CMAP) Amplitude and Decrement search | Baseline and then every 6 months until end of the study, up to 24 months | 
| Change from baseline of Biomarkers of SMA progression | SMN mRNA and protein analysis, SMA exploratory biomarkers (e.g. mRNA, DNA profiling, RNA profiling, proteomic profiling) | Baseline and then every 6 months until end of the study, up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SMA, Spinal Muscular Atrophy, Neuromuscular disease