Multicenter ALS Imaging Study

NCT ID: NCT06735014

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 90 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-15
• Study Completion Date: 2028-08-31

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.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Participants with ALS

Adults with early stage ALS

Magnetic Resonance Imaging

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs

Plasma neurofilament light chain (NfL) quantification

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo a blood draw for the quantification of plasma neurofilament light chain

Participants without ALS

Control participants free from neurological disease

Magnetic Resonance Imaging

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs

Plasma neurofilament light chain (NfL) quantification

Intervention Type: DIAGNOSTIC_TEST

Participants will undergo a blood draw for the quantification of plasma neurofilament light chain

Interventions

Magnetic Resonance Imaging

Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs

Intervention Type: DIAGNOSTIC_TEST

Plasma neurofilament light chain (NfL) quantification

Participants will undergo a blood draw for the quantification of plasma neurofilament light chain

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Food and Drug Administration (FDA)

FED

Sponsor Role: collaborator

Minnesota Office of Higher Education

OTHER_GOV

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pramod Pisharady, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Florida

Gainesville, Florida, United States

Site Status: RECRUITING

Northwestern University

Evanston, Illinois, United States

Site Status: NOT_YET_RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Melisa Bailey, MS

Role: CONTACT

baile807@umn.edu

612-624-4911

Facility Contacts

Jennifer Steshyn, MABMH, CCRP

Role: primary

Emma Schmidt

Role: primary

Melisa Bailey, MS

Role: primary

baile807@umn.edu

Other Identifiers

CMRR-2024-32796

Identifier Type: -

Identifier Source: org_study_id