ALS Spinal Cord Gray and White Matter Study

Spinal Cord Gray and White Matter Imaging in Amyotrophic Lateral Sclerosis

This study aims to measure in vivo the spinal cord gray and white matter in patients with Amyotrophic Lateral Sclerosis and healthy persons that match the patients' age and sex using rAMIRA imaging, a novel Magnetic Resonance Imaging (MRI) method. Patients and healthy control persons prospectively undergo MRI examinations, clinical examinations including assessments of disability, and tests of muscle force using hand held dynamometry. Serum markers of neuro-axonal injury are also assessed.

Examinations for patients and healthy control persons are scheduled every six months over a time span of two years.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Diagnostic test: Magnetic Resonance Imaging

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Regina Schlaeger, PD Dr.; Phone Number: 0041 61 328 67 49; Email: regina.schlaeger@usb.ch
• Study Contact Backup: Name: Janina Wendebourg, Dr.; Phone Number: 0041 61 556 57 99; Email: janina.wendebourg@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Regina Schlaeger, PD Dr.; Phone Number: 0041 61 328 67 49; Email: regina.schlaeger@usb.ch
    • Contact: Janina Wendebourg, Dr.; Phone Number: 0041 556 57 99; Email: janina.wendebourg@usb.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

All patients diagnosed with possible, probable, and definite Amyotrophic Lateral Sclerosis acc. to the El Escorial aged 18 years or older can participate in this study. Healthy control persons are chosen to individually match the included patients. Additionally, patients with other motor neuron diseases (not ALS) will be included.

Description

Inclusion Criteria (patients):

1. 18 years or older
2. neurologist-confirmed possible, probable or definite ALS acc. to El Escorial criteria
3. at baseline: able to lie in an MRI scanner for one hour

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. severe cervical spinal stenosis or other relevant disease of the spine or spinal cord that may interfere with study procedures or that may impact the cord segments imaged in this study
4. other severe chronic disease
5. pregnancy
6. general contraindications against MRI scanning (e.g. metal implants, pacemakers)
7. not able to read the patient information due to language barriers (patient information in English and French may be provided)
8. major cognitive deficit impacting the ability to read and understand the patient information and/or to follow the instructions of the study personnel

Inclusion criteria (healthy control persons):

1. 18 years or older
2. able to lie in MRI scanner for one hour

Exclusion criteria (healthy control persons):

1. neurological or neuromuscular conditions
2. other severe chronic disease
3. pregnancy
4. general contraindications against MRI scanning (e.g. metal implants, pacemakers)
5. relevant cervical spinal canal stenosis or other relevant disease of the spine or spinal cord that may interfere with study procedures or that may impact the cord segments imaged in this study
6. not able to read the patient information due to language barriers (patient information in English and French may be provided)

Inclusion criteria (patients with Motor Neuron Diseases other than ALS):

1. 18 years or older
2. neurologist-confirmed Motor Neuron Disease (not ALS)
3. able to lie in MRI scanner for one hour

Exclusion criteria (patients with Motor Neuron Diseases other than ALS):

1. other severe neurologic disease
2. other severe chronic disease
3. pregnancy
4. general contraindications against MRI scanning (e.g. metal implants, pacemakers)
5. relevant cervical spinal canal stenosis or other relevant disease of the spine or spinal cord that may interfere with study procedures or that may impact the cord segments imaged in this study
6. not able to read the patient information due to language barriers (patient information in English and French may be provided)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Amyotrophic Lateral Sclerosis; Patients with a possible, probable, or definite diagnosis of Amyotrophic Lateral Sclerosis according to the El Escorial Criteria.	Diagnostic test: Magnetic Resonance Imaging; Magnetic Resonance Imaging of the spinal cord using radially acquired Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA)
Healthy Control Persons; Healthy control persons matching the ALS patient group in sex and age	Diagnostic test: Magnetic Resonance Imaging; Magnetic Resonance Imaging of the spinal cord using radially acquired Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA)
Patients with other Motor Neuron Diseases; Patients with Motor Neuron Diseases other than ALS	Diagnostic test: Magnetic Resonance Imaging; Magnetic Resonance Imaging of the spinal cord using radially acquired Averaged Magnetization Inversion Recovery Acquisitions (rAMIRA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spinal Cord Gray Matter Baseline	Spinal cord gray matter cross-sectional area in mm2	baseline
Spinal Cord Gray Matter 6 month follow-up	Spinal cord gray matter cross-sectional area in mm2	6 month follow-up
Spinal Cord Gray Matter 12 month follow-up	Spinal cord gray matter cross-sectional area in mm2	12 month follow-up
Spinal Cord Gray Matter 18 month follow-up	Spinal cord gray matter cross-sectional area in mm2	18 month follow-up
Spinal Cord Gray Matter 24 month follow-up	Spinal cord gray matter cross-sectional area in mm2	24 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spinal Cord White Matter	Spinal cord white matter cross-sectional area in mm2	baseline, months 6, 12, 18 and 24
Spinal Cord Total Area	Total spinal cord cross-sectional area in mm2	baseline, months 6, 12, 18 and 24
ALS Functional Rating Scale	ALS Functional Rating Scale (ALSFRS-R)	baseline, months 6, 12, 18 and 24
Neurofilament Light Chain Levels	Neurofilament Light Chain Levels (pg/ml)	baseline, months 6, 12, 18 and 24
Sniff nasal inspiratory pressure	Sniff nasal inspiratory pressure (SNIP) (cmH2O)	baseline, months 6, 12, 18 and 24
Segmental Muscle Force	Segmental Muscle Force assessed by hand-held dynamometry (N)	baseline, months 6, 12, 18 and 24
MUNIX	Motor Unit Number Index (MUNIX) in selected muscles	baseline, months 6, 12, 18 and 24

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 9, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Spinal Cord Magnetic Resonance Imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: ALS_SC_MRI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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