Multicenter ALS Imaging Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Magnetic Resonance Imaging, Plasma neurofilament light chain (NfL) quantification.
- Who it may be relevant to
- Registry conditions: Amyotrophic Lateral Sclerosis, ALS. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Multicenter Longitudinal Imaging in ALS for Disease Biomarker Development
Overview
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.
Detailed description
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.
Interventions
- Diagnostic test Magnetic Resonance Imaging
Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs - Diagnostic test Plasma neurofilament light chain (NfL) quantification
Participants will undergo a blood draw for the quantification of plasma neurofilament light chain
Primary outcome measures
- Fiber Density [Time frame: Baseline, 3 months, 6 months, 12 months]
- Fiber Cross-Section [Time frame: Baseline, 3 months, 6 months, 12 months]
- Orientation Dispersion [Time frame: Baseline, 3 months, 6 months, 12 months]
- Intracellular Volume Fraction [Time frame: Baseline, 3 months, 6 months, 12 months]
- Free Water [Time frame: Baseline, 3 months, 6 months, 12 months]
- Cortical Thickness [Time frame: Baseline, 3 months, 6 months, 12 months]
- Spinal Cord Cross-Sectional Area [Time frame: Baseline, 3 months, 6 months, 12 months]
- Spinal Cord Corticospinal Tract (CST) Fractional Anisotropy (FA) [Time frame: Baseline, 3 months, 6 months, 12 months]
Secondary outcome measures (4)
- Plasma neurofilament light (NfL) quantification [Time frame: Baseline, 3 months, 6 months, 12 months]
- ALS Functional Rating Scale, Revised (ALSFRS-R) [Time frame: Baseline, 3 months, 6 months, 12 months]
- Edinburgh Cognitive and Behavioural Screen (ECAS) [Time frame: At 3-month visit (optional)]
- Penn Upper Motor Neuron Score [Time frame: Baseline]
Eligibility criteria
For participants with ALS:
- < 36 months since onset of symptoms
- Definite, probable, lab-supported probable, or possible ALS by El Escorial criteria OR definite, probable, or possible ALS per Awaji-Shima criteria OR meets Gold Coast criteria
- Forced vital capacity within the last 90 days ≥ 60% of the predicted value
- Able to consent for themselves
- Able to read and speak English
- Clear of any contraindications for MRI
Exclusion criteria
- Individuals will be excluded if they have any condition that makes MRI unsafe or if they are unable to comply with instructions.
- All participants will undergo a neurologic examination at enrollment. Control participants with clinically significant abnormal findings on neurological examination will be excluded from the study.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
United States · 3 centers
- University of Florida — Gainesville
- Northwestern University — Evanston
- University of Minnesota — Minneapolis
Identifiers
NCT: NCT06735014 · CMRR-2024-32796