Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis

The overall purpose of this research is to determine whether new macromolecular measures optimized for whole brain (gray matter and white matter) magnetic resonance imaging (MRI), predict neuro-cognitive impairment in multiple sclerosis (MS) patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: Multiple Sclerosis; MS
• Intervention / Treatment: Diagnostic test: MRI; Diagnostic test: Neuropsychological Testing

Detailed Description

MRI is a vital component of a MS work-up, providing noninvasive evidence of MS lesions, detecting active inflammatory lesions, and measuring brain atrophy to assess neurodegeneration. Recent years of MRI research have generated strong evidence of gray matter (GM) involvement in MS, resulting in the reclassification of MS as a whole-brain disease. Similar to white matter (WM), a primary target of MS pathology in GM is myelin, the protective sheath insulating the penetrating axons within GM and extending brain connectivity all the way to the neuronal bodies.

This aim of this research is to examine if the associations between imaging measures of GM disease and cognitive performance can establish GM-based imaging correlates predicting the disease course and accurately assessing treatment results.

This observational research will enroll adults diagnosed with MS both with and without cognitive impairment. Subjects will be asked to complete a single research visit that includes the administration of a MRI scan and a neuro-cognitive testing session.

• Study Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin, Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults diagnosed with MS both with and without evidence of cognitive impairment.

Healthy controls will be recruited from the MRI Volunteer Database (2017-0004, PI: Reeder)

Description

Inclusion Criteria:

• Clinically definite MS
• Adult age 18 to 60

Exclusion Criteria:

• Contraindication to MRI
• Changes in MS therapy in the last 6 months
• Less than 6 weeks after relapse or corticosteroid use
• Currently taking medication that may affect cognition (e.g. donepezil, rivastigmine, adderall)
• History of significant alcohol or drug abuse
• Current or recent significant migraines
• Confounding neurological or cognitive disorders or deficits (stroke, Parkinson's disease, Alzheimer's disease, epilepsy)
• Sensory or physical impairments that might interfere significantly with cognitive testing
• History of developmental or learning disability or attention-deficit/hyperactivity disorder.\

Exclusion Criteria for Healthy Controls:

• history of alcohol/drug abuse
• history of migraines
• developmental or learning disability/attention-deficit/hyperactivity disorder
• currently pregnant/breastfeeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitive Impairment; Adults diagnosed with MS that have evidence of cognitive decline.	Diagnostic test: MRI; The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.; Other Names: Functional MRI; Diagnostic test: Neuropsychological Testing; A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.
No Cognitive Impairment; Adults diagnosed with MS that have no evidence of cognitive decline.	Diagnostic test: MRI; The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.; Other Names: Functional MRI; Diagnostic test: Neuropsychological Testing; A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.
Healthy Controls; Healthy adult volunteers will form a control group matched for age, gender, education, handedness	Diagnostic test: MRI; The MRI protocol will include conventional testing for MS lesion detection and functional MR imaging to localize associated neurocognitive domains in each subject.; Other Names: Functional MRI; Diagnostic test: Neuropsychological Testing; A comprehensive battery of neuropsychological tests will be administered to assess memory, new learning, spatial processing and higher executive function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of macromolecular proton content (MPC) by Magnetic resonance imaging	Macromolecular Proton Fraction (MPF) is calculated from several specially acquired MR images and is characterized by high degree of sensitivity and specificity to tissue macromolecules, which are the main target of pathological process in neurodegenerative diseases including multiple sclerosis (MS). These properties of MPF are in contrast with standard MR images, which are primarily sensitive to tissue water molecules.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive performance as measured by Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests	The results of Minimal Assessment of Cognitive Function in MS (MACFIMS) battery of neuropsychological (NP) tests will form the secondary outcome measure. The NP scores will be correlated with MPF to study association between macromolecular tissue damage and neurocognitive performance.	24 hours
Neurocognitive performance as measured by the Montreal Cognitive Assessment (MoCA) score	Neurocognitive performance will be measured by Montreal Cognitive Assessment. MoCA scores range from 0 to 30, higher values corresponding to better cognitive performances.	24 hours

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Investigators: Principal Investigator: Alexey Samsonov, PhD, UW Madison

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 2020-0310; A539300 (Other Identifier: UW- Madison); SMPH/RADIOLOGY/RADIOLOGY (Other Identifier: UW Madison); 1R01EB027087-01 (U.S. NIH Grant/Contract); Protocol Version 4/29/2021 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No