An observational study in Amyotrophic Lateral Sclerosis and ALS, sponsored by University of Minnesota. Recruiting at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by University of Minnesota · Observational
This is a multi-site study of ALS participants and healthy controls who will undergo brain and cervical spine MRIs and NfL blood testing at up-to 4 time points over the course of a year. The primary goal is to identify objective biomarkers of disease progression that are biologically relevant, linearly progressive, and sensitive to change.
Recent developments in Magnetic Resonance Imaging (MRI), biophysical modeling, and computing have improved the sensitivity of imaging metrics to detect disease-related changes in the central nervous system in neurological disorders. This improved sensitivity has paved the way for utilizing these metrics as potential biomarkers of disease, in particular, to measure disease progression over short durations.
The investigators hypothesize that the multimodal analysis of MRI biomarkers (microstructure and morphology) from the brain and spine will improve sensitivity to detect disease-related changes over durations as short as 3 to 6 months. The hypothesis is based on prior work detecting longitudinal changes in brain microstructure over 6 months in an ALS cohort with modest change in functional measures over that time, and that a multimodal analysis combining brain and spine MRI measures can improve disease diagnosis accuracy.
In this project, the investigators will establish the scalability, sensitivity over shorter durations, and overall clinical trial readiness of these metrics through a three-site study. The investigators also propose to improve the sensitivity of imaging metrics by combining multiple complementary measures from the brain and spine in a longitudinal multimodal statistical framework. Additionally, the investigators will demonstrate how these imaging metrics correlate with fluid biomarkers and functional progression measures.
Upon completion of the project, the investigators anticipate that the enhanced sensitivity of our proposed longitudinal MRI biomarkers will have an impact on ALS treatment by providing novel surrogate markers as potential outcome measures for clinical trials. The expected increased effect size will also reduce the cohort size needed to conduct trials, thereby increasing their feasibility. Beyond the scope of clinical trials, these multimodal MRI biomarkers will serve as an objective measure of upper motor neuron degeneration at the single patient level. The MRI measures will also be cross validated with fluid biomarkers and will contribute to efforts to stratify ALS patients into clinically homogeneous cohorts.
Participants will be asked to complete 4 study visits over a 12-month period, with visits at baseline, 3 months, 6 months, and 12 months. Participants will receive an exam by a neurologist, blood draw, and MRI scan and will be asked to answer surveys about their medical history and ALS symptoms. Participants will be compensated for each visit via a prepaid card. Non-local participants living ≥100 miles from the research facility will be partially compensated for travel.
981 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 283 are open to participants now.
This study's planned enrollment of 90 is below the median of 106 across 265 observational studies indexed under Amyotrophic Lateral Sclerosis.
Browse Amyotrophic Lateral Sclerosis studies →University of Minnesota is the lead sponsor of 1,184 studies on the registry; 195 are open to participants now.
Of its 132 completed or terminated interventional studies of FDA-regulated products, 91 (69%) have results posted.
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Adults with early-stage ALS
For participants with ALS:
Exclusion Criteria:
Adults with early stage ALS
Diagnostic Test: Magnetic Resonance Imaging · Diagnostic Test: Plasma neurofilament light chain (NfL) quantification
Control participants free from neurological disease
Diagnostic Test: Magnetic Resonance Imaging · Diagnostic Test: Plasma neurofilament light chain (NfL) quantification
Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs
Participants will undergo a blood draw for the quantification of plasma neurofilament light chain
Fiber Density
This measure comes from the biophysical model used in brain imaging and is collected using MRI. It refers to the volume of the intra-axonal compartment per unit volume of the tissue. As this is a fraction it does not have a unit.
Time frame: Baseline, 3 months, 6 months, 12 months
Fiber Cross-Section
This measure comes from the biophysical model used in brain imaging and is collected using MRI. It refers to the change it fiber cross-section at the fiber bundle level when undergoing spatial normalization. This measure does not have a unit.
Time frame: Baseline, 3 months, 6 months, 12 months
Orientation Dispersion
This measure comes from the biophysical model used in brain imaging and is collected using MRI. Orientation dispersion is a measure of the uncertainty in the estimation of the fiber bundle orientation. It varies from 0 to 1 and does not have a unit. Higher values indicate greater uncertainty in estimation.
Time frame: Baseline, 3 months, 6 months, 12 months
Intracellular Volume Fraction
This measure comes from the biophysical model used in brain imaging and is collected using MRI. It is the proportion of the imaging voxel occupied by intracellular compartments. This ratio varies from 0 to 1 and does not have a unit. Larger values indicate greater density of intracellular compartments.
Time frame: Baseline, 3 months, 6 months, 12 months
Free Water
This measure comes from the biophysical model used in brain imaging and is collected using MRI. It represents the fractional volume of the free-water compartment. This is a ratio and it does not have a unit.
Time frame: Baseline, 3 months, 6 months, 12 months
Cortical Thickness
This measure is collected using MRI. It is the thickness of the cortical gray matter and is measured in millimeters.
Time frame: Baseline, 3 months, 6 months, 12 months
Spinal Cord Cross-Sectional Area
This measure is collected using MRI. It is the area of the spinal cord cross-section measured in millimeter square.
Time frame: Baseline, 3 months, 6 months, 12 months
Spinal Cord Corticospinal Tract (CST) Fractional Anisotropy (FA)
This measure is collected using MRI. It is a dimensionless scalar value between 0 and 1, indicating the degree of anisotropy (directionality) of water diffusion in the spinal cord's corticospinal tract. Higher values indicate higher anisotropy.
Time frame: Baseline, 3 months, 6 months, 12 months
Plasma neurofilament light (NfL) quantification
Plasma NfL quantification will be reported in units of pg/ml.
Time frame: Baseline, 3 months, 6 months, 12 months
ALS Functional Rating Scale, Revised (ALSFRS-R)
The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 (can't do) to 4 (normal ability). Individual item scores are summed to produce a reported score of between 0=worst and 48=best.
Time frame: Baseline, 3 months, 6 months, 12 months
Edinburgh Cognitive and Behavioural Screen (ECAS)
The ECAS is a 20-minute assessment of language, memory, verbal fluency, executive function, visuospatial function, and social cognition, which produce a number of subscales with a maximum total score of 136. Higher scores indicate better functioning.
Time frame: At 3-month visit (optional)
Penn Upper Motor Neuron Score
The Penn Upper Motor Neuron Score (PUMNS) is a 28-item scale that measures upper motor neuron (UMN) signs in amyotrophic lateral sclerosis (ALS). The scale ranges from 0 (normal) to 32 (for widespread/severe UMN involvement) and evaluates the bulbar region (scores 0-4), upper limbs (scores 0-14), and lower limb (scores 0-14). Higher scores indicate greater disease burden.
Time frame: Baseline
Plan to share: Yes — We plan to publish deidentified and preprocessed data from this study through public neuroimaging repositories. To facilitate the reproduction of our findings, we will also publish the deidentified data used to produce the figures and tables in our publications. We will keep the names and other identifying information of participants confidential.
No publications or documents are linked to this record.
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