Clinical trial NCT06735014: Multicenter ALS Imaging Study
Official title: Multicenter Longitudinal Imaging in ALS for Disease Biomarker Development
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
ALS
Keywords: Magnetic Resonance Imaging
MRI
ALSFRS-R
ECAS
plasma neurofilament light
NfL
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
name: Minnesota Office of Higher Education
First posted: 2024-12-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults with early-stage ALS

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

* \< 24 months since onset of symptoms
* Definite, probable, laboratory-supported probable, or possible ALS by El Escorial criteria OR definite, probable, or possible ALS by Awaji-Shima 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.

Primary outcomes:
measure: Fiber Density
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Fiber Cross-Section
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Orientation Dispersion
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Intracellular Volume Fraction
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Free Water
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Cortical Thickness
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Spinal Cord Cross-Sectional Area
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Spinal Cord Corticospinal Tract (CST) Fractional Anisotropy (FA)
timeFrame: Baseline, 3 months, 6 months, 12 months
Secondary outcomes:
measure: Plasma neurofilament light (NfL) quantification
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: ALS Functional Rating Scale, Revised (ALSFRS-R)
timeFrame: Baseline, 3 months, 6 months, 12 months
measure: Edinburgh Cognitive and Behavioural Screen (ECAS)
timeFrame: At 3-month visit (optional)
measure: Penn Upper Motor Neuron Score
timeFrame: Baseline
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Pramod Pisharady, PhD
role: PRINCIPAL_INVESTIGATOR
References: