Amyotrophic Lateral SclerosisNCT06735014
Multicenter ALS Imaging Study
An observational study of Amyotrophic Lateral Sclerosis and ALS, run by University of Minnesota at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, ALS
- What is being tested?
- Magnetic Resonance Imaging and Plasma neurofilament light chain (NfL) quantification
- How many people
- 90 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Sep 2024to 31 Aug 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with early-stage ALS
Who may be able to join
None listed.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Northwestern University
Evanston, Illinois, 60208
Elizabeth Delehanty
Senda Ajroud-Driss, MD
- Recruiting
University of Florida
Gainesville, Florida, 32608
Amy Holland, BSN, RN
James Wymer, MD, FAAN
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Melisa Bailey, MS, baile807@umn.edu
David Walk, MD
About this study
Official title: Multicenter Longitudinal Imaging in ALS for Disease Biomarker Development
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.
Read the 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
- Being tested
- Magnetic Resonance Imaging, Plasma neurofilament light chain (NfL) quantification
- Keywords
- Magnetic Resonance Imaging, MRI, ALSFRS-R, ECAS, plasma neurofilament light, NfL
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnetic Resonance ImagingDiagnostic test
Participants will undergo 3T MRI scanning of the brain and cervical spine MRIs
Plasma neurofilament light chain (NfL) quantificationDiagnostic test
Participants will undergo a blood draw for the quantification of plasma neurofilament light chain
| Study group | Role | What they receive |
|---|---|---|
| Participants with ALS | Adults with early stage ALS Receives: Diagnostic Test: Magnetic Resonance Imaging; Diagnostic Test: Plasma neurofilament light chain (NfL) quantification | |
| Participants without ALS | Control participants free from neurological disease Receives: Diagnostic Test: Magnetic Resonance Imaging; Diagnostic Test: Plasma neurofilament light chain (NfL) quantification |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 3 months, 6 months, 12 months
Secondary outcomes (4)
Plasma neurofilament light (NfL) quantification
Plasma NfL quantification will be reported in units of pg/ml.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2024
- Study start15 Sep 2024
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA), Minnesota Office of Higher Education
- Responsible party
- Sponsor
- Investigators
- Pramod Pisharady, PhD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06735014
- Sponsor's protocol ID
- CMRR-2024-32796
- Status last verified
- May 2026
- First submitted
- 22 Nov 2024
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Longitudinal Imaging in ALS for Disease Biomarker Development
- ClinicalTrials.gov ID
- NCT06735014
- Acronym / sponsor ID
- CMRR-2024-32796
- Conditions
- Amyotrophic Lateral Sclerosis, ALS
- Keywords
- Magnetic Resonance Imaging, MRI, ALSFRS-R, ECAS, plasma neurofilament light, NfL
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA), Minnesota Office of Higher Education
- Study start
- 15 Sep 2024 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 16 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with ALS | – | Diagnostic Test: Magnetic Resonance Imaging, Diagnostic Test: Plasma neurofilament light chain (NfL) quantificationAdults with early stage ALS |
| Participants without ALS | – | Diagnostic Test: Magnetic Resonance Imaging, Diagnostic Test: Plasma neurofilament light chain (NfL) quantificationControl participants free from neurological disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with early-stage ALS
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnetic Resonance ImagingParticipants will undergo 3T MRI scanning of the brain and cervical spine MRIs | Diagnostic test | Participants with ALS, Participants without ALS |
| Plasma neurofilament light chain (NfL) quantificationParticipants will undergo a blood draw for the quantification of plasma neurofilament light chain | Diagnostic test | Participants with ALS, Participants without ALS |
Primary outcome
Fiber Density
Time frame: Baseline, 3 months, 6 months, 12 months
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.
Fiber Cross-Section
Time frame: Baseline, 3 months, 6 months, 12 months
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.
Orientation Dispersion
Time frame: Baseline, 3 months, 6 months, 12 months
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.
Intracellular Volume Fraction
Time frame: Baseline, 3 months, 6 months, 12 months
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.
Free Water
Time frame: Baseline, 3 months, 6 months, 12 months
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.
Cortical Thickness
Time frame: Baseline, 3 months, 6 months, 12 months
This measure is collected using MRI. It is the thickness of the cortical gray matter and is measured in millimeters.
Spinal Cord Cross-Sectional Area
Time frame: Baseline, 3 months, 6 months, 12 months
This measure is collected using MRI. It is the area of the spinal cord cross-section measured in millimeter square.
Spinal Cord Corticospinal Tract (CST) Fractional Anisotropy (FA)
Time frame: Baseline, 3 months, 6 months, 12 months
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.
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pramod Pisharady, PhD principal investigator
University of Minnesota
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyotrophic Lateral Sclerosis and ALS, run by University of Minnesota at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melisa Bailey, MS (612-624-4911, baile807@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fiber Density (time frame: Baseline, 3 months, 6 months, 12 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.