Characterization of New Phenotypes of Patients With Spinal Muscular Atrophy Treated With SMN Restoring Therapy

NCT ID: NCT06321965

Last Updated: 2026-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-24

Study Completion Date

2029-01-24

Brief Summary

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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.

Detailed Description

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Conditions

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Spinal Muscular Atrophy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Prospective, longitudinal, multicenter, international study
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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SMA patient treated with SRT

Patients aged 0-15 with SMA type 1, 2 or 3, treated with TRS (nusinersen/risdiplam/onasemnogene abeparvovec/other).

Group Type EXPERIMENTAL

evaluation of muscle function

Intervention Type OTHER

Myogrip (≥ 6 years): precise dynamometric measurement of gripping force, measuring force in Newton up to 90kg with 0.01kg resolution. It's evaluated at D0, M6, M12, M18, and M24 Myopinch (≥ 6 years) : measure thumb-index force up to 15 kg with a resolution of 0.001 kg using a precision sensor equipped with two steel distance blades. It's evaluated at D0, M6, M12, M18, and M24

First-line cognitive assessment

Intervention Type OTHER

Vineland-II (All patients) : is a scale for assessing adaptive behaviors. will be carried out during the telephone call at M1/V2.

All tests are evaluated at D0, and M18 :

Bayley-4 language part (\< 42 months) PVSE (≥ 4 years) CELF-5 (≥ 5 years) Conners-3 (≥ 6 years) AQ (≥ 4 years), EQ (≥ 11 years)

M-CHAT-R (\< 4 years) :

SRS-2 (≥ 2 years)

second-line cognitive assessment

Intervention Type OTHER

In the event of positive cognitive screening at D0 or M18, a second-line cognitive assessment will be carried out at a subsequent visit. A list of tests is proposed below, but will be adapted according to the tests available at each center.

* EVALO BB (0-2 years) or EVALO (2-6 years) or full CELF-5 (5-18 years) following positive screening in the communication domain of first-line tests (Vineland II communication domain, Bayley 4, CELF-5 pragmatic profile)
* FEE and DSM-5 diagnostic criteria for ADHD (from age 6 only) following positive screening in the attention and executive functions domain of first-line tests (Conners 3, BRIEF)
* M-CHAT-R/F (\< 4 years) or SCQ (≥ 4 years) and ADOS-2 (≥ 12 years) following a positive screening in the area of social cognition and autistic traits on first-line tests (Vineland II, M-CHAT-R, SRS-2, EQ, AQ).

Cardiac evaluation

Intervention Type OTHER

All tests are evaluated at D0, M12, and M24 :

Electrocardiogram (ECG) : This examination will be carried out in accordance with the 12 leads recording the following parameters: verification of sinus rhythm, P wave, PR interval, QRS complex (interval), ST segment, T wave, QT complex, heart rate.

Cardiac ultrasound: Non-invasive ultrasound will focus on the following parameters measured from 2-dimensional images, to look for cardiomyopathy and/or structural abnormality:

* end-diastolic/end-systolic diameter/left ventricular ejection fraction
* Septal wall thickness / left ventricular posterior wall
* Fractional shortening 24-hour Holter-ECG : This examination consists of a continuous test recording the heart rhythm for 24 hours.

MRI

Intervention Type RADIATION

Cerebral MRI : Performed at D0, only for patients with ASI type 1 ≥ 6 years, or younger patients for whom the investigator considers that the examination can be performed without sedation or general anesthesia. It will include sequences:

* 3D T1, gradient echo, 1.1 mm voxel, sagittal acquisition
* axial T2, spin-echo, slice thickness 4 mm
* 3D FLAIR, spin-echo, 1 mm voxel, sagittal acquisition Muscular MRI: performed at V1/J0, and V6/M24. The examination will include water-fat imaging (Dixon) in full-body, 3D mode, with proton density weighting and millimeter resolution.

Assessment of activity and muscle fatigue

Intervention Type OTHER

Syde® : evaluated at D0, M6, M12, M24. Patients aged 2 and over will receive the Syde® wearable device to collect their daily activities.

Muscular endurance tests (≥ 6 years) : evaluated at D0, M12, M24 ( only one of 3 tests based on motor function level) oESNHPT : In this test, patients are asked to walk a 10-meter path. oESBBT : In this test, patients have to move 10 blocks over a partition. oESWT: In this test, patients must repeatedly place and remove 9 sticks in 9 holes.

PedsQL Fatigue (≥ 2 years): evaluated at D0, M12, M24. Scale designed to measure fatigue in patients with acute and chronic conditions, as well as in healthy school and community populations.

Fatigue rating scale (≥ 6 years): evaluated at D0, M12, M24. The fatigue assessment scale has 11 numerical points ranging from 0 to 10. The patient is asked to give a rating that best reflects his or her perception of fatigue at that particular moment.

Assessment of bulbar function

Intervention Type OTHER

DDD-pNMD (≥ 2 years) : evaluated at D0, M6, M12, M18, and M24, is a list of 9 questions used by doctors to screen for dysphagia and dysarthria.

NdSSS (All Patients) : evaluated at D0, M6, M12, M18, and M24, is an 8-level scale for assessing swallowing.

TOMASS-c : (≥ 4 years of age, in patients able to eat solids safely, after assessment of the risk of a false route by the speech therapist): this is a score designed to assess mastication when eating a cracker. Age-dependent standards exist for different types of cracker.

\- Fluid intake test (\> 110 cm, in patients able to drink a liquid safely, after assessment of the risk of a false route by the speech therapist): swallowing limit.

Evaluation of body composition and metabolism

Intervention Type OTHER

Food survey : The dietary survey questionnaire will be sent to parents at D0 and M18. Parents will be asked to complete it for 3 days before the M6 and M24.

Bioelectrical impedancemetry: Evaluated at M6 and M24. Renal ultrasound: Evaluated at M6, is a non-invasive examination that analyzes the appearance of the kidney and urinary tract.

Dual-energy X-ray absorptiometry (DXA) : Evaluated at M6, it measures body composition using spectral imaging, including fat mass, lean mass and bone mineral density.

Fibroscan : Evaluated at M6 and M24. This examination uses pulse elastography to measure liver elasticity, which provides information on the presence of hepatic fibrosis, and sound attenuation, which provides information on the presence of liver fat overload.

Indirect calorimetry : Evaluated at M6. This device enables precise measurement of Resting Energy Expenditure , Respiratory Quotient and metabolic substrate oxidation.

Questionnaires

Intervention Type OTHER

SMAIS : The questionnaire has been developed specifically for ASI. At D0, M6, M12, M18 and M24.

HUI2 : specializes in preference-based measures of health-related quality of life. At D0, M6, M12, M18 and M24.

Peds QL : is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. At D0, M6, M12, M18 and M24.

Neuromuscular module : 17 disease-related items. It is evaluated at D0, M6, M12, M18 and M24.

Family impact module : It measures parents' reported physical, emotional, social and cognitive functioning, communication and concerns. At D0, M12, and M24.

ASI cost questionnaire: At visit 1 (D0): This questionnaire, completed by the parents, includes information on occupation, parents' working hours and any reduction in them due to the child's pathology, the number of working days missed by the parents or school days missed by the child, and disability-related costs.

Biocollection

Intervention Type BIOLOGICAL

A blood bio collection (optional) will be offered to patients at D0, M6 , M12, M18, M24.

Patients receiving intrathecal injections will also be offered the opportunity to participate in a CSF (cerebrospinal fluid) biocollection (optional).

Skinfold measurement

Intervention Type OTHER

The tricipital point should be marked on the posterior aspect of the arm, on the midline of the tricipital muscle, midway between the acromion and the radius. At D0, M6, M12, M18 and M24

Interventions

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evaluation of muscle function

Myogrip (≥ 6 years): precise dynamometric measurement of gripping force, measuring force in Newton up to 90kg with 0.01kg resolution. It's evaluated at D0, M6, M12, M18, and M24 Myopinch (≥ 6 years) : measure thumb-index force up to 15 kg with a resolution of 0.001 kg using a precision sensor equipped with two steel distance blades. It's evaluated at D0, M6, M12, M18, and M24

Intervention Type OTHER

First-line cognitive assessment

Vineland-II (All patients) : is a scale for assessing adaptive behaviors. will be carried out during the telephone call at M1/V2.

All tests are evaluated at D0, and M18 :

Bayley-4 language part (\< 42 months) PVSE (≥ 4 years) CELF-5 (≥ 5 years) Conners-3 (≥ 6 years) AQ (≥ 4 years), EQ (≥ 11 years)

M-CHAT-R (\< 4 years) :

SRS-2 (≥ 2 years)

Intervention Type OTHER

second-line cognitive assessment

In the event of positive cognitive screening at D0 or M18, a second-line cognitive assessment will be carried out at a subsequent visit. A list of tests is proposed below, but will be adapted according to the tests available at each center.

* EVALO BB (0-2 years) or EVALO (2-6 years) or full CELF-5 (5-18 years) following positive screening in the communication domain of first-line tests (Vineland II communication domain, Bayley 4, CELF-5 pragmatic profile)
* FEE and DSM-5 diagnostic criteria for ADHD (from age 6 only) following positive screening in the attention and executive functions domain of first-line tests (Conners 3, BRIEF)
* M-CHAT-R/F (\< 4 years) or SCQ (≥ 4 years) and ADOS-2 (≥ 12 years) following a positive screening in the area of social cognition and autistic traits on first-line tests (Vineland II, M-CHAT-R, SRS-2, EQ, AQ).

Intervention Type OTHER

Cardiac evaluation

All tests are evaluated at D0, M12, and M24 :

Electrocardiogram (ECG) : This examination will be carried out in accordance with the 12 leads recording the following parameters: verification of sinus rhythm, P wave, PR interval, QRS complex (interval), ST segment, T wave, QT complex, heart rate.

Cardiac ultrasound: Non-invasive ultrasound will focus on the following parameters measured from 2-dimensional images, to look for cardiomyopathy and/or structural abnormality:

* end-diastolic/end-systolic diameter/left ventricular ejection fraction
* Septal wall thickness / left ventricular posterior wall
* Fractional shortening 24-hour Holter-ECG : This examination consists of a continuous test recording the heart rhythm for 24 hours.

Intervention Type OTHER

MRI

Cerebral MRI : Performed at D0, only for patients with ASI type 1 ≥ 6 years, or younger patients for whom the investigator considers that the examination can be performed without sedation or general anesthesia. It will include sequences:

* 3D T1, gradient echo, 1.1 mm voxel, sagittal acquisition
* axial T2, spin-echo, slice thickness 4 mm
* 3D FLAIR, spin-echo, 1 mm voxel, sagittal acquisition Muscular MRI: performed at V1/J0, and V6/M24. The examination will include water-fat imaging (Dixon) in full-body, 3D mode, with proton density weighting and millimeter resolution.

Intervention Type RADIATION

Assessment of activity and muscle fatigue

Syde® : evaluated at D0, M6, M12, M24. Patients aged 2 and over will receive the Syde® wearable device to collect their daily activities.

Muscular endurance tests (≥ 6 years) : evaluated at D0, M12, M24 ( only one of 3 tests based on motor function level) oESNHPT : In this test, patients are asked to walk a 10-meter path. oESBBT : In this test, patients have to move 10 blocks over a partition. oESWT: In this test, patients must repeatedly place and remove 9 sticks in 9 holes.

PedsQL Fatigue (≥ 2 years): evaluated at D0, M12, M24. Scale designed to measure fatigue in patients with acute and chronic conditions, as well as in healthy school and community populations.

Fatigue rating scale (≥ 6 years): evaluated at D0, M12, M24. The fatigue assessment scale has 11 numerical points ranging from 0 to 10. The patient is asked to give a rating that best reflects his or her perception of fatigue at that particular moment.

Intervention Type OTHER

Assessment of bulbar function

DDD-pNMD (≥ 2 years) : evaluated at D0, M6, M12, M18, and M24, is a list of 9 questions used by doctors to screen for dysphagia and dysarthria.

NdSSS (All Patients) : evaluated at D0, M6, M12, M18, and M24, is an 8-level scale for assessing swallowing.

TOMASS-c : (≥ 4 years of age, in patients able to eat solids safely, after assessment of the risk of a false route by the speech therapist): this is a score designed to assess mastication when eating a cracker. Age-dependent standards exist for different types of cracker.

\- Fluid intake test (\> 110 cm, in patients able to drink a liquid safely, after assessment of the risk of a false route by the speech therapist): swallowing limit.

Intervention Type OTHER

Evaluation of body composition and metabolism

Food survey : The dietary survey questionnaire will be sent to parents at D0 and M18. Parents will be asked to complete it for 3 days before the M6 and M24.

Bioelectrical impedancemetry: Evaluated at M6 and M24. Renal ultrasound: Evaluated at M6, is a non-invasive examination that analyzes the appearance of the kidney and urinary tract.

Dual-energy X-ray absorptiometry (DXA) : Evaluated at M6, it measures body composition using spectral imaging, including fat mass, lean mass and bone mineral density.

Fibroscan : Evaluated at M6 and M24. This examination uses pulse elastography to measure liver elasticity, which provides information on the presence of hepatic fibrosis, and sound attenuation, which provides information on the presence of liver fat overload.

Indirect calorimetry : Evaluated at M6. This device enables precise measurement of Resting Energy Expenditure , Respiratory Quotient and metabolic substrate oxidation.

Intervention Type OTHER

Questionnaires

SMAIS : The questionnaire has been developed specifically for ASI. At D0, M6, M12, M18 and M24.

HUI2 : specializes in preference-based measures of health-related quality of life. At D0, M6, M12, M18 and M24.

Peds QL : is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. At D0, M6, M12, M18 and M24.

Neuromuscular module : 17 disease-related items. It is evaluated at D0, M6, M12, M18 and M24.

Family impact module : It measures parents' reported physical, emotional, social and cognitive functioning, communication and concerns. At D0, M12, and M24.

ASI cost questionnaire: At visit 1 (D0): This questionnaire, completed by the parents, includes information on occupation, parents' working hours and any reduction in them due to the child's pathology, the number of working days missed by the parents or school days missed by the child, and disability-related costs.

Intervention Type OTHER

Biocollection

A blood bio collection (optional) will be offered to patients at D0, M6 , M12, M18, M24.

Patients receiving intrathecal injections will also be offered the opportunity to participate in a CSF (cerebrospinal fluid) biocollection (optional).

Intervention Type BIOLOGICAL

Skinfold measurement

The tricipital point should be marked on the posterior aspect of the arm, on the midline of the tricipital muscle, midway between the acromion and the radius. At D0, M6, M12, M18 and M24

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

0 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Pediatric Rehabilitation Service - L'Escale Mother and Child Hospital

Bron, Rhone, France

Site Status RECRUITING

CHRU of Brest

Brest, , France

Site Status NOT_YET_RECRUITING

Pediatric Neurology and Resuscitation Raymond-Poincare Hospital

Garche, , France

Site Status NOT_YET_RECRUITING

Pediatric Neurology Swynghedauw Hospital

Lille, , France

Site Status NOT_YET_RECRUITING

Marseille University Hospital - Timone Hospital Department of Pediatric Neurology - Specialized Pediatrics and Child Medicine

Marseille, , France

Site Status NOT_YET_RECRUITING

I-Motion Pediatric Clinical Trial Platform Armand Trousseau Hospital

Paris, , France

Site Status NOT_YET_RECRUITING

Hautepierre Hospital - Mother and Child Hospital

Strasbourg, , France

Site Status NOT_YET_RECRUITING

Department of Pediatrics - Neurology and Infectious Diseases Toulouse University Hospital - Children's Hospital

Toulouse, , France

Site Status NOT_YET_RECRUITING

Countries

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France

Central Contacts

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Laure LE GOFF, PI

Role: CONTACT

04.72.12.95.04 ext. +33

Tiphanie GINHOUX

Role: CONTACT

04.27.85.77.23 ext. +33

Facility Contacts

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Laure LE GOFF, PI

Role: primary

04.72.12.95.04 ext. +33

Juliette ROPARS, Dr

Role: primary

02.98.22.33.89 ext. +33

Susana QUIJANO-ROY, Pr

Role: primary

01.47.10.79.16 ext. +33

Jean-Baptiste DAVION, Dr

Role: primary

03.20.44.58.31 ext. +33

Brigitte CHABROL, Pr

Role: primary

04.91.38.68.08 ext. +33

Andreea SEFERIAN, Dr

Role: primary

01.71.73.80.50 ext. +33

Vincent LAUGEL, Pr

Role: primary

03.88.12.77.43 ext. +33

Claude CANCES, Pr

Role: primary

05.34.55.74.08 ext. +33

Other Identifiers

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69HCL22_0599

Identifier Type: -

Identifier Source: org_study_id

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