French Register of Patients With Spinal Muscular Atrophy

Spinal Muscular Atrophy Clinical Trial

— SMA  

Official title:

French Register of Patients With Spinal Muscular Atrophy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04177134
• Other study ID #: APHP190245
• Secondary ID: N° IDRCB: 2019-A
• Status: Recruiting
• Start date: January 31, 2020
• Est. completion date: January 31, 2029

Study information

• Verified date: March 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Susana Quijano-Roy, MD, PhD
• Phone: +33147107890
• Email: susana.quijano-roy[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The primary objectives of the study are to obtain clinically meaningful data on survival and outcomes of all the patients with spinal muscular atrophy (SMA) 5q types 1 through 4 (according to international classification), being followed in the reference centers of the disease in France between September 1, 2016 and August 31, 2024. The registry will collect retrospectively and prospectively the longitudinal data of the long-term follow-up for child and adult patients, under real life conditions of current medical practice, in order to document the clinical evolution of patients (survival, motor, respiratory, orthopedic and nutritional), the conditions of use of the treatments, the mortality rates of treated and untreated patients, the tolerance of the treatments, adverse events in order to better define their places in the therapeutic strategy.

Description:

As secondary objectives, the study aims:

• to estimate the frequencies of patients with SMA 5q types 1 through 4 who have being treated in the reference centers between September 1 2016 and August 31 2024;

• to describe overall demographic, familial, clinical, biological, and genetic characteristics of SMA 5q patients treated in all regions of France, by the type of SMA (type 1,2,3, and 4);

• to study the impact of proactive and symptomatic medical interventions (bracing, IPPB devices) and medications (vaccinations, anti-infectious, digestive, nutritional supplements) in the evolution of patients;

• to study the long-term evolution (survival, motor and respiratory functions, spinal shape, growth and nutritional function) of SMA 5q in treated and untreated populations, by new available therapies, throughout the register;

• to study mortality rate of SMA 5q in treated and untreated populations, by new available therapies, throughout the register;

• to identify and document the different therapeutic strategies by sub-populations and by discontinuation or follow-up of treatments;

• to evaluate prognostic factors of responses to therapies;

• to study the tolerance of treatments by type of treatments, by type of SMA and overall tolerance (including adverse events);

• to estimate the costs of care for SMA 5q patients in different groups (types, ages);

• to provide needful elements to evaluate the health care costs for the disease;

• to study the autonomy and the quality of life of patients depending on different therapeutic strategies;

• to study the impact of the disease on caregivers;

• to facilitate development of scientific research on SMA in the conduct of trials on new therapeutic strategies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: January 31, 2029
• Est. primary completion date: January 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days and older

Eligibility

Inclusion Criteria:

• Genetically confirmed SMA 5q patients through 1 to 4 types treated in reference centers in France between September 1, 2016 and August 31, 2024.

• for prospective study: inform consent form signed by patient.

• for retrospective data: information form with non-opposition have been given to participant.

• Covered by a health insurance.

Exclusion Criteria:

• Other type of SMA (not 5q).

• Under guardianship or curatorship.

• Unable to understand french language.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Locations

Country	Name	City	State
France	Unité neuromusculaire, Service de Neurologie et Réanimation Pédiatrique, (French neuromuscular reference network (FILNEMUS), Hôpital Raymond Poincaré,	Garches

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Motor functional development or status	SMA Type 1 until 2 years of age: change of HINE (Hammersmith Infant Neurological Examination) score; Children: change in Vignos and Brooke scores (level of upper and Lower extremities autonomy); Adults: change in Walton & Boston scores (level of upper and Lower extremities autonomy)	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Primary	Motor function scores	For children = 2 years: change of CHOP INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) score will be evaluated; For children between 2 and 5 years, ambulatory or not: Change of total MFM-20 (Motor Function Measure 20) score will be evaluated. Change of 3 dimension scores will be evaluated: D1 (start and transfers station), D2 (axial and proximal motricity) and D3 (distal including the upper limb); For children children > 6 years and adults, ambulatory or not: Change of total MFM-32 (Motor Function Measure 32) score will be evaluated. Change of 3 dimension scores will be evaluated: D1 (start and transfers station), D2 (axial and proximal motricity) and D3 (distal including the upper limb).; For ambulatory individuals: added 6MWT (6 minutes walking test)	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Primary	Yearly changes of morbi-mortality-vital events	Events of hospitalizations, recurrent infections, fractures, complications and death.	9 years
Primary	Respiratory events	Onset of respiratory support or change in the mode and time (including intubations).	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Primary	Digestive-nutritional events	Digestive events, onset of nutritional support or change in the mode and time	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Primary	Yearly changes of spinal events	Onset of spinal deformity, or increment of 5° or more in the Cobb angle (examination in supine position without brace ; if sitting possible, examination in the upright position, with or without brace or with or without implant (surgery)	9 years
Secondary	Frequency	Frequencies of patients with SMA 5q of type 1,2,3 and 4 cared in the reference centres between September 1 2016 and August 31 2024.	through study completion, an average of 9 year
Secondary	Responses to the treatments (nusinersen and salbutamol)	Responses of the primary outcome measures to the therapies (salbutamol, nusinersen, onasemnogene, risdiplam)	1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Spinal status	Evolution of scoliosis (Cobb angle) in the preoperative period (patients treated vs not treated with Garches brace): first and last Cobb angle (and ages)	1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Impact of spinal surgery techniques in scoliosis	Impact of spinal surgery techniques in scoliosis (presurgical and last post surgical Cobb angle)	1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Mortality	For treated and untreated patients. Rate of mortality will be assessed at 1,2 and 5 years.	at 1, 2 and 5 years
Secondary	Pulmonary function	Forced vital capacity (FVC) will be evaluated at least once per year for children > 5 years, by specifying the posture of realization of the test, lying vs sitting.	at 6 months
Secondary	Respiratory muscles performance	Peak expiratory and inspiratory pressures will be evaluated if possible for children > 5 years (MEP, MIP, PF, SNIP (sniff nasal inspiratory pressure)	at 6 months
Secondary	Pulmonary function	PCF (peak cough flow) will be evaluated at least once per year for children > 5 years, by specifying the posture of realization of the test, lying vs sitting.	at 6 months
Secondary	Cardiological parameter	ECG abnormality will be evaluated by Holter ECG 24h: P Wave, QRS Complex, QT Interval	through study completion, an average of 9 year
Secondary	Cardiological function and anatomy	Anatomic abnormalities will be evaluated by echocardiography.	through study completion, an average of 9 year
Secondary	Biomarkers	Change of biomarkers: Neurofilaments and CPK	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Patient's quality of life: PedsQL (Pediatric Quality of Life Inventory) Child report	Questionary as the "PedsQL Child report" will be used to evaluate patient's quality of life. Total Scale Score: 0.88 Child Self-Report; 0.90 Parent Proxy-Report.	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Patient's quality of life: PedsQL parent report concerning child	Questionary as the "PedsQL parent report concerning child" will be used to evaluate patient's quality of life. Total Scale Score: 0.88 Child Self-Report; 0.90 Parent Proxy-Report.	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Patient's quality of life: QoL-gNMD for adult	Questionary as "QoL-gNMD for adult" (Quality of Life in genetic Neuromuscular Disease) will be used to evaluate patient's quality of life.	baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Caregiver burden assessement	Questionnaire as "Work Productivity and Activity Impairment Questionnaire SMAv2" will be completed once a year by a member of neuromuscular center or patients or their relatives.	at baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year
Secondary	Caregiver burden assessement	Questionnaire as "FICD+4 Burden Interview Questionnaire" will be completed once a year by a member of neuromuscular center or patients or their relatives.; FICD (Family Impact of Childhood Disability)+4 Burden Interview Questionnaire: the multidimensional measurements to assess the impacts on time, expenses, work, relationships and health of caregiver.	at baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year