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French Register of Patients With Spinal Muscular Atrophy (SMA)

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ClinicalTrials.gov Identifier: NCT04177134
Recruitment Status : Recruiting
First Posted : November 26, 2019
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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.

Condition or disease
Spinal Muscular Atrophy

Detailed 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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration: 9 Years
Official Title: French Register of Patients With Spinal Muscular Atrophy
Actual Study Start Date : January 31, 2020
Estimated Primary Completion Date : January 31, 2029
Estimated Study Completion Date : January 31, 2029





Primary Outcome Measures :
  1. Motor functional development or status [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    • 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)

  2. Motor function scores [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    • 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)

  3. Yearly changes of morbi-mortality-vital events [ Time Frame: 9 years ]
    Events of hospitalizations, recurrent infections, fractures, complications and death.

  4. Respiratory events [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Onset of respiratory support or change in the mode and time (including intubations).

  5. Digestive-nutritional events [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Digestive events, onset of nutritional support or change in the mode and time

  6. Yearly changes of spinal events [ Time Frame: 9 years ]
    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)


Secondary Outcome Measures :
  1. Frequency [ Time Frame: through study completion, an average of 9 year ]
    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.

  2. Responses to the treatments (nusinersen and salbutamol) [ Time Frame: 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Responses of the primary outcome measures to the therapies (salbutamol, nusinersen, onasemnogene, risdiplam)

  3. Spinal status [ Time Frame: 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Evolution of scoliosis (Cobb angle) in the preoperative period (patients treated vs not treated with Garches brace): first and last Cobb angle (and ages)

  4. Impact of spinal surgery techniques in scoliosis [ Time Frame: 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Impact of spinal surgery techniques in scoliosis (presurgical and last post surgical Cobb angle)

  5. Mortality [ Time Frame: at 1, 2 and 5 years ]
    For treated and untreated patients. Rate of mortality will be assessed at 1,2 and 5 years.

  6. Pulmonary function [ Time Frame: at 6 months ]
    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.

  7. Respiratory muscles performance [ Time Frame: at 6 months ]
    Peak expiratory and inspiratory pressures will be evaluated if possible for children > 5 years (MEP, MIP, PF, SNIP (sniff nasal inspiratory pressure)

  8. Pulmonary function [ Time Frame: at 6 months ]
    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.

  9. Cardiological parameter [ Time Frame: through study completion, an average of 9 year ]
    ECG abnormality will be evaluated by Holter ECG 24h: P Wave, QRS Complex, QT Interval

  10. Cardiological function and anatomy [ Time Frame: through study completion, an average of 9 year ]
    Anatomic abnormalities will be evaluated by echocardiography.

  11. Biomarkers [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Change of biomarkers: Neurofilaments and CPK

  12. Patient's quality of life: PedsQL (Pediatric Quality of Life Inventory) Child report [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    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.

  13. Patient's quality of life: PedsQL parent report concerning child [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    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.

  14. Patient's quality of life: QoL-gNMD for adult [ Time Frame: baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    Questionary as "QoL-gNMD for adult" (Quality of Life in genetic Neuromuscular Disease) will be used to evaluate patient's quality of life.

  15. Caregiver burden assessement [ Time Frame: at baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]
    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.

  16. Caregiver burden assessement [ Time Frame: at baseline, 1 year, 2 year, 3 year, 4 year, 5 year, 6 year, 7 year, 8 year and 9 year ]

    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.



Biospecimen Retention:   Samples Without DNA
Blood sampling for biomarkers, with DNA.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
1000 SMA 5q patients of type 1, 2, 3 and 4, followed or diagnosed between September 1, 2016 and August 31, 2024. It is estimated that approximately 50% of patients will be children.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04177134


Contacts
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Contact: Susana Quijano-Roy, MD, PhD +33147107890 susana.quijano-roy@aphp.fr

Locations
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France
Unité neuromusculaire, Service de Neurologie et Réanimation Pédiatrique, (French neuromuscular reference network (FILNEMUS), Hôpital Raymond Poincaré, Recruiting
Garches, France, 92380
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Susana Quijano-Roy, MD, PhD Unité neuromusculaire, Service de Neurologie et Réanimation Pédiatrique, Hôpital Raymond Poincaré, 92380 Garches, FRANCE

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04177134    
Other Study ID Numbers: APHP190245
N° IDRCB: 2019-A01161-56 ( Other Identifier: ANSM )
First Posted: November 26, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
spinal muscular atrophy
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases