ALS Spinal Cord Gray and White Matter Study

Study Overview
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Brief Summary
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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.

Official Title
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Spinal Cord Gray and White Matter Imaging in Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Diagnostic Test: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (patients): 18 years or older neurologist-confirmed possible, probable or definite ALS acc. to El Escorial criteria at baseline: able to lie in an MRI scanner for one hour Exclusion Criteria (patients): active other neurological or neuromuscular condition explaining the symptoms or a significant part of it other neurological or neuromuscular conditions interfering with the examinations 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 other severe chronic disease pregnancy general contraindications against MRI scanning (e.g. metal implants, pacemakers) not able to read the patient information due to language barriers (patient information in English and French may be provided) 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): 18 years or older able to lie in MRI scanner for one hour Exclusion criteria (healthy control persons): neurological or neuromuscular conditions other severe chronic disease pregnancy general contraindications against MRI scanning (e.g. metal implants, pacemakers) 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 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): 18 years or older neurologist-confirmed Motor Neuron Disease (not ALS) able to lie in MRI scanner for one hour Exclusion criteria (patients with Motor Neuron Diseases other than ALS): other severe neurologic disease other severe chronic disease pregnancy general contraindications against MRI scanning (e.g. metal implants, pacemakers) 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 not able to read the patient information due to language barriers (patient information in English and French may be provided)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, Spinal Cord Magnetic Resonance Imaging