Type 2 Spinal Muscular Atrophy, Type 3 Spinal Muscular Atrophy
Conditions
Keywords
SMA, Spinal Muscular Atrophy, Neuromuscular disease
Brief summary
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.
Interventions
OTHERStrength, function and activity measurements
OTHERMuscle MRI
OTHERElectrophysiology measurements
OTHERBlood sampling for biomarker analysis
Sponsors
Institut Roche
Institut de Myologie, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of muscle strength | Baseline and then every 6 months until end of the study, up to 24 months | Study-specific assessments: Grip and pinch strength |
| Change from baseline of motor function | Baseline and then every 6 months until end of the study, up to 24 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of skeletal muscle nuclear magnetic resonance (NMR) imaging (MRI) | Baseline and then every 12 months until the end of the study, up to 24 months | Muscle volume changes, intramuscular fatty infiltration progression, indices of disease activity (only for Paris and Strasbourg sites and for patients older than 4 years) |
| Change from baseline of respiratory function | Baseline and then every 6 months until end of the study, up to 24 months | Study-specific assessments: Pulmonary function tests |
| Change from baseline of Biomarkers of SMA progression | Baseline and then every 6 months until end of the study, up to 24 months | SMN mRNA and protein analysis, SMA exploratory biomarkers (e.g. mRNA, DNA profiling, RNA profiling, proteomic profiling) |
| Change from baseline of electrophysiology measurements | Baseline and then every 6 months until end of the study, up to 24 months | Compound Motor Action Potential (CMAP) Amplitude and Decrement search |
| Change from baseline of physical activity of upper limbs movements | Baseline and then every 6 months until end of the study, up to 24 months | Quantity and duration of movements, time of inactivity during the day |
Countries
Belgium, France, Germany
Outcome results
None listed