Spinal Cord Gray Matter Imaging in Spinal Muscular Atrophy

Spinal Muscular Atrophy Type II Clinical Trial

Official title:

Spinal Cord Gray Matter Imaging - a Novel Biomarker for Spinal Muscular Atrophy - a Pilot Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06137612
• Other study ID #: SMA_SC_Imaging_1
• Status: Enrolling by invitation
• Start date: August 17, 2020
• Est. completion date: September 15, 2025

Study information

• Verified date: November 2023
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to measure the spinal cord gray matter in patients with spinal muscular atrophy (SMA) type II and III in comparison with age- and sex-matched healthy controls (HC) using rAMIRA (radially sampled averaged magnetization inversion recovery acquisitions) imaging, a novel MRI (Magnetic Resonance Imaging) method. Patient and HC undergo MRI examinations, clinical/neurological (handheld dynamometry) and electrophysiological investigations (MUNIX, Motor Unit Number Index). Serum markers of neuro-axonal and astrocytic injury are also assessed.

Description:

Patients with the diagnosis of 5q-SMA (spinal muscular atrophy) types II or III (confirmed by genetic testing) will be recruited. Healthy age and sex-matched controls will also be investigated.

Patients will be neurologically investigated at the Neurology Policlinic, University Hospital Basel, including standard muscle force measurements on the British Medical Council (BMC) grade, and quantitative muscle force tests by hand held dynamometer of selected muscles.

All patients will also complete the SMA functional rating scale (SMA-FRS). Age and sex matched healthy controls will also undergo a standardized neurological examination to ensure that no other neurological condition is present that could potentially interfere with the test results.

All participants will be scanned on the same 3 Tesla MR-Scanner (Magnetom PRISMA, Siemens Healthineers) at the University Hospital Basel. The protocol includes axial 2D rAMIRA imaging at selected levels of cervical and thoracic spinal cord at the intervertebral disc levels perpendicular to the spinal cord, and diffusion tensor imaging (DTI) at selected positions, a standard diagnostic high-resolution T2w sequence of the spinal cord and a high-resolution T1w structural imaging of the brain for cortical/subcortical volumetry.

Serum biomarkers will also be evaluated including serum neurofilament light chain (NfL) levels .

MUNIX is an electrophysiological method that is used in clinical routine in many neuromuscular centers to quantitate the number of functioning motor units. Patients and controls will undergo MUNIX testing .

Patients will be examined by a professional physiotherapist to assess the Motor Function Measure (MFM), Revised Hammersmith Scale for SMA, Revised Upper Limb Module, time to rise from the floor, and 6 minutes walk test.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 52
• Est. completion date: September 15, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 11 Years and older

Eligibility

Inclusion Criteria (patients)

1. 11 years or older

2. Informed consent by the participants or, in children below the age of legal consent, by a legally authorized representative

3. genetically confirmed diagnosis of 5q-SMA (Types II or III)

Exclusion Criteria (patients):

1. active other neurological or neuromuscular condition explaining the symptoms or a significant part of it

2. other neurological or neuromuscular conditions interfering with the examinations

3. other severe chronic disease

4. pregnancy

5. general contraindications against MRI scanning (e.g. pacemakers)

6. not able to understand the patient information due to language barriers

7. In the event of a participant incapable of judgment, symptoms showing that the participant is unwilling to participate in the study will result in the participant being excluded from participation

Inclusion Criteria (healthy volunteers)

1. participants will be selected to be age-and sex-matched to the patients

2. 11 years or older

3. Informed consent by the participants or, in children below the age of legal consent, by a legally authorized representative

Exclusion Criteria (healthy volunteers):

1. active neurological or neuromuscular condition

2. other neurological or neuromuscular conditions interfering with the examinations

3. other severe chronic disease

4. pregnancy

5. general contraindications against MRI scanning (e.g. pacemakers)

6. not able to understand the patient information due to language barriers

7. In the event of a participant incapable of judgment, symptoms showing that the participant is unwilling to participate in the study will result in the participant being excluded from participation

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy Type II
• Spinal Muscular Atrophy Type III

Intervention

Diagnostic Test:
• MRI
axial 2D rAMIRA (radially sampled averaged magnetization inversion recovery acquisitions) imaging at selected levels of cervical and thoracic spinal cord at the intervertebral disc levels perpendicular to the spinal cord.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel	BS

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spinal cord gray matter atrophy	Difference in spinal cord gray matter (GM) cross-sectional area in mm2 between SMA patients and age and sex matched HC subjects	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and segmental quantitative muscle force (in Newton) in SMA patients	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and SMA-FRS-R Score in SMA patients	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and RULM Score in SMA patients	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and HFSME Score in SMA patients	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and MFM Score in SMA patients	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and serum NfL(pg/ml)	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and MUNIX (Index)	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and 6MWT	baseline
Secondary	Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and time to rise from the floor	baseline