Spinal Cord Gray Matter Imaging in Spinal Muscular Atrophy

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Spinal Muscular Atrophy Type II; Spinal Muscular Atrophy Type III
• Intervention / Treatment: Diagnostic test: MRI

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with SMA; Patients with SMA type II and III	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.
Healthy controls; Age- and sex-matched HC	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and segmental quantitative muscle force (in Newton) in SMA patients	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and SMA-FRS-R Score in SMA patients	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and RULM Score in SMA patients	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and HFSME Score in SMA patients	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and MFM Score in SMA patients	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and serum NfL(pg/ml)	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and MUNIX (Index)	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and 6MWT	baseline
Associations	Cross-sectional associations between spinal cord GM areas (in mm2) and time to rise from the floor	baseline

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): September 15, 2025

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Estimated): November 17, 2023

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood
• Other Study ID Numbers: SMA_SC_Imaging_1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No