MR Imaging in Spinal Muscular Atrophy (SMA) as a biomarker for disease progressio

Completed

• Conditions: Spinal Muscular Atrophy; 10029299; 10029317

• Registration Number: NL-OMON47876
• Lead Sponsor: niversitair Medisch Centrum Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2020-06-03
• Study Completion: 2020-07-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 63

Inclusion Criteria

1 a. SMA patients
i. Patients with SMA from the treatment naive cohort will be included following the predefined criteria:
1) a diagnosis of SMA type 2 or 3, diagnosed on clinical grounds and confirmed by homozygous deletion of the SMN1 gene;
2) given oral and written informed consent
ii. Patients with SMA eligible for therapy will be included following the predefined criteria:
1) a diagnosis of SMA type 1-4, diagnosed on clinical grounds and confirmed by homozygous deletion of the SMN1 gene;
2) given oral and written consent by:
- patient and parents or legal guardians when patient is between 12-15 years
- parents or legal guardians when patient is under 12 years
iii. Aged 6 years and older
b. Healthy control subjects without manifest diagnosis of motor neuron disease or myopathy
i. given oral and written informed consent
2. Capable of thoroughly understanding the study information given

Exclusion Criteria

1. Tracheostomy, tracheostomal ventilation of any type, (non)-invasive ventilation
2. Any intoxication or medication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of motor neuron disease.
3. Presence of pronounced swallowing disorders or orthopnoea (which make it dangerous to lie supine in the MRI scanner)
4. Contra-indication for 3 Tesla MRI (as established by the radiology department)
5. Pregnancy
6. Forced Vital Capacity >15% postural change between sitting and supine or symptoms of nocturnal hypoventilation (recurrent morning headaches, nightsweats, orthopneu).
7. Presence of non-MRI compatible material in the body
8. Claustrophobia

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Muscle fat fraction as quantified with DIXON method (based on a chemical<br /><br>shift method for water-fat separation.<br /><br><br /><br>2. Changes in tissue composition of muscle, as quantified with T2 mapping<br /><br>(based on the transverse relaxation time of water in tissue).<br /><br><br /><br>3. Tissue architecture visualized using Diffusion Tensor Imaging (DTI), further<br /><br>enabling 3D reconstruction of tissue and quantification of microstructural<br /><br>properties (based on fiber tractography (FT) and fractional anisotropy (FA)<br /><br>together with mean diffusity (MD)).<br /><br><br /><br>4. Structures of spinal cord and nerve roots visualized with MR images and DTI<br /><br>for qualitative and quantitative assessment.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The structural and functional changes will be regarded in relation to genotype<br /><br>(= SMN2 copynumber, a disease modifier) and clinical parameters.<br /><br>Clinical parameters include: age, gender, age at onset of disease, Forced Vital<br /><br>Capacity, disease severity (as measured by the SMA-FRS questionnaire and<br /><br>clinical scores; MRC and dynamometry score and HFMSE combined with upper limb<br /><br>module) and disease duration.</p><br>