Clinical trial NCT06321965: Characterization of New Phenotypes of Patients with Spinal Muscular Atrophy Treated with SMN Restoring Therapy
Official title: Characterization of New Phenotypes of Patients with Spinal Muscular Atrophy Treated with SMN Restoring Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Muscular Atrophy
Keywords: Natural history
Spinal Muscular atrophy (SMA)
Risdiplam
Onasemnogene abeparvovec
Nusinersen
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2024-03-20
Enrollment: 60
Sex: ALL
Minimum age (years): 0
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, longitudinal, multicenter, international study
Primary purpose: OTHER

Brief summary: With the advent of new treatments for ASI, new phenotypes are emerging. The investigators propose to describe these new phenotypes by prospectively following children with ASI of all types treated with TRS and aged under 16 for 2 years.

The investigators also propose to evaluate potential assessment tools to determine whether they are relevant for monitoring this population, either routinely or for future clinical trials. The investigators also aim to collect the total costs associated with ASI in order to propose a first prospective medico-economic study in France.


Eligibility criteria: Inclusion Criteria:

* Genetically confirmed infantile or juvenile spinal muscular atrophy
* Treated with a therapy that restores SMN protein expression (e.g. nusinersen, risdiplam, onasemnogene abeparvovec)
* Aged 0 to 15 years inclusive
* Informed consent signed by both parent(s)/legal guardian(s) and patient's assent
* Affiliated or beneficiary of a health insurance plan\*. \* for inclusion in France

Exclusion Criteria:

* Other condition likely to interfere significantly with ASI assessment and clearly unrelated to the disease
* Other associated neurological disease
* Current pregnancy or breast-feeding (a pregnancy test will also be performed at inclusion).

Please note that patients with a specific contraindication to MRI (i.e. metallic foreign body, claustrophobia and other reasons determined by the investigators) will be allowed to participate in the study, but MRI will not be performed.

Primary outcomes:
measure: Markers of disease progression and description of different phenotypes, at : muscular and functional
timeFrame: Every 6 months from inclusion (Day 0, Month6, Month12, Month18, Month24)
measure: Markers of disease progression and description of different phenotypes, at : muscular and functional
timeFrame: Every 6 months from inclusion (Day 0, Month 6, Month 12, Month 18, Month 24)
measure: Markers of disease progression and description of different phenotypes, at : muscular and functional
timeFrame: Every 6 months from inclusion (Day 0, Month 6, Month 12, Month 18, Month 24)
measure: Markers of disease progression and description of different phenotypes, at : muscular and functional
timeFrame: Every 6 months from inclusion (Day 0, Month 6, Month 12, Month 18, Month 24)
measure: Markers of disease progression and description of different phenotypes, at : muscular and functional
timeFrame: Every 6 months from inclusion (Day 0, Month 6, Month 12, Month 18, Month 24)
measure: Markers of disease progression and description of different phenotypes, at : Fatigue
timeFrame: Syde: At Day 0, Month 6, Month 12 and Month 24
measure: Markers of disease progression and description of different phenotypes, at : Fatigue
timeFrame: Endurance test (≥ 6 years)
measure: Markers of disease progression and description of different phenotypes, at : Fatigue
timeFrame: at Day 0, Month 12 and Month 24
measure: Markers of disease progression and description of different phenotypes, at Orthopaedic level
timeFrame: Joint amplitudes at Day 0, Month 6, Month 12 and Month 24
measure: Markers of disease progression and description of different phenotypes, at Orthopaedic level
timeFrame: Clinic and spinal radiography at Day 0, Month 12,Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at Orthopaedic level
timeFrame: at Day 0, Month 24+/- Month 6, Month 12, Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: Vineland-II
timeFrame: At Month 1
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: Bayley-4
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: BRIEF (Behavioral Rating Inventory of Executive Function)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: Conners-3
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: CELF-5 (Language and communication assessment battery)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: EQ (Empathy quotient), AQ (Autism Quotient)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: M-CHAT-R (Modified Checklist for Autism in Toddlers)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: SRS-2 (Social Responsiveness Scale, Second Edition)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the cognitive level: PVSE (Basic visuo-spatial perception)
timeFrame: At Day 0 and Month 18
measure: Markers of disease progression and description of different phenotypes, at the brain level
timeFrame: At Day 0
measure: Markers of disease progression and description of different phenotypes, at Cardiology level
timeFrame: At Day 0 +/- Month 12, Month 24
measure: Markers of disease progression and description of different phenotypes, at metabolic level : Anthropometric measurement trends
timeFrame: Anthropometric measurements at Day 0, Month 6, Month 12, Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at metabolic level :
timeFrame: Food survey at Month 6, Month 24
measure: Markers of disease progression and description of different phenotypes, at metabolic level : fractures
timeFrame: at Day 0, Month 6, Month 12, Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at metabolic level : renal ultrasound
timeFrame: at Month 6
measure: Markers of disease progression and description of different phenotypes, at metabolic level : Absorptiometry (DXA)
timeFrame: at Month 6
measure: Markers of disease progression and description of different phenotypes, at metabolic level: Calorimetry
timeFrame: at Month 6
measure: Markers of disease progression and description of different phenotypes, at metabolic level : Impedancemetry
timeFrame: at Month 6 and Month 24
measure: Markers of disease progression and description of different phenotypes, at metabolic level : Fibroscan
timeFrame: At Month 6 and Month 24
measure: Markers of disease progression and description of different phenotypes, at biological analysis
timeFrame: At Day 0, Month 6, Month 12, Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at In terms of quality of life and autonomy
timeFrame: PedsQL family impact at Day 0, Month 12, Month 24
measure: Markers of disease progression and description of different phenotypes, at In terms of quality of life and autonomy
timeFrame: HUI-2, generic PedsQL and neuromuscular module at Day 0, Month 6, Month 12, Month 18 and Month 24
measure: Markers of disease progression and description of different phenotypes, at respiratory level : Chest/head circumference ratio (PT/PC ratio) (up to 3 years)
timeFrame: at Day 0, Month 6, Month 12, Month 18 and Month 24
measure: Markers of disease progression and description of different phenotypes, at respiratory level : Chest/head circumference ratio (PT/PC ratio)
timeFrame: at Day 0, Month 6, Month 12, Month 18 and Month 24
measure: Markers of disease progression and description of different phenotypes, at respiratory level : O2 saturation and nocturnal TcPCO2
timeFrame: at Day 0, Month 12, Month 24
measure: Markers of disease progression and description of different phenotypes, at respiratory level: Respiratory function tests (≥ 6 years)
timeFrame: at Day 0, Month 12, Month 24
measure: Markers of disease progression at respiratory level
timeFrame: points (Day 0, between Day 0-Month 12, between Month 12 and Month 24)
measure: Markers of disease progression and description of different phenotypes, at bulbar level (Evaluation of dysphagia and dysarthria): DDD-pNMD (Diagnostic list for Dysphagia and Dysarthria in pediatric NeuroMuscular Disorders)
timeFrame: At Day 0, Month 6, Month 12, Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at bulbar level (Evaluation of dysphagia and dysarthria): NdSSS (Neuromuscular Disease Swallowing Status Scale).
timeFrame: At Day 0, Month 6, Month 12, Month 18, Month 24
measure: Markers of disease progression and description of different phenotypes, at the level of Characteristics at inclusion: age of patient
timeFrame: At Day 0
measure: Markers of disease progression and description of different phenotypes, at the level of Characteristics at inclusion : patient gender
timeFrame: At Day 0
measure: Markers of disease progression and description of different phenotypes, at the level of Characteristics at inclusion: SMA TYPE
timeFrame: At Day 0
measure: Markers of disease progression and description of different phenotypes, at the level of Characteristics at inclusion: number of copy
timeFrame: At Day 0
measure: Markers of disease progression and description of different phenotypes, at the level of Characteristics at inclusion: treatment
timeFrame: At Day 0
Secondary outcomes:
Other outcomes:
Locations:
city: Bron
country: France
facility: Pediatric Rehabilitation Service - L'Escale Mother and Child Hospital
state: Rhone
city: Brest
country: France
facility: CHRU of Brest
city: Garche
country: France
facility: Pediatric Neurology and Resuscitation Raymond-Poincare Hospital
city: Lille
country: France
facility: Pediatric Neurology Swynghedauw Hospital
city: Marseille
country: France
facility: Marseille University Hospital - Timone Hospital Department of Pediatric Neurology - Specialized Pediatrics and Child Medicine
city: Paris
country: France
facility: I-Motion Pediatric Clinical Trial Platform Armand Trousseau Hospital
city: Strasbourg
country: France
facility: Hautepierre Hospital - Mother and Child Hospital
city: Toulouse
country: France
facility: Department of Pediatrics - Neurology and Infectious Diseases Toulouse University Hospital - Children's Hospital
Study officials:
References: