Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis (MS)

Linking Cognitive Functioning to Multimodal Imaging in Multiple Sclerosis

Multiple sclerosis (MS) is the most common progressive neurologic disorder to occur in adults of working-age. Despite longstanding recognition of cognitive impairment as a symptom of MS, two obstacles in measurement have limited understanding its biological basis, and therefore identifying targeted options for management. First is the absence of a sensitive and precise measure of cognitive impairment. Second is the absence of an index of disease status linked to brain pathophysiology and cognitive performance. This project overcomes both obstacles to link cognitive impairment to MS disease biomarkers. The absence of a sensitive and precise measure of cognitive impairment, along with the absence of an index of disease status linked to brain pathophysiology and cognitive performance, limits the understanding of the biological basis for multiple sclerosis (MS). This project overcomes both obstacles to link cognitive function to MS disease biomarkers, and provides preliminary evaluation of a disease modifying therapy (Tecfidera) for preserving cognitive function.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis; Cognition Disorders
• Intervention / Treatment: Diagnostic test: Siemens Biograph mMR (molecular MR); Diagnostic test: fMRI; Diagnostic test: Diffusion Spectrum Imaging (DSI)

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

20 MS participants and 10 healthy controls. However, the data analysis is planned for 15 MS participants and 10 healthy control participants. It is expected that 15 MS subjects and 10 healthy controls will complete 12 months.

Description

Inclusion Criteria:

1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
2. Male and Female subjects between 18 and 45 years
3. WRAT-4 Reading [127] standard score > 85
4. Able to undergo neuroimaging data collection procedures. For MS Participants
5. Definite diagnosis of RRMS [128]
6. EDSS of 0 to 6.0
7. Adequate vision as as reported by the participant (with correction if applicable)
8. Clinically prescribed Tecfidera, Tysabri or Ocrevus therapy by treating neurologist, with first dose being within 3 months + 14 days from baseline visit
9. At baseline visit, concurrent medications to be kept constant over three months prior to data collection visits
10. No relapse or steroids in previous month

Exclusion Criteria:

1. Unable or unwilling to provide informed consent.
2. Beck Depression Inventory-Fast Screen (BDI-FS) [129, 130] score of 4 or more
3. Current alcohol or other substance use disorder
4. Primary psychiatric disorder that would adversely influence ability to participate
5. Other neurological condition associated with cognitive impairment (e.g., epilepsy, brain injury)
6. Other serious uncontrolled medical condition (e.g., cancer or acute myocardial infarction)
7. Learned English language after 12 years of age

8. For low absolute low lymphocyte count (ALC), USPI guidance will be utilized.

   For MS participants:

9. Lemtrada, Cladribine, Mitoxantrone

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MS Patients; Definite diagnosis of RRMS	Diagnostic test: Siemens Biograph mMR (molecular MR); 5mCi of the radiotracer FDG administered intravenously as a bolus over 30s. After injection, emission data will be collected for 60 min,; Diagnostic test: fMRI; High-resolution T1-weighted structural image will be acquired using an MP2RAGE sequence. Subject will beasked to look at the cross hair on a screen andnot fixate on any one thought.; Diagnostic test: Diffusion Spectrum Imaging (DSI); DSI allows for more accurate characterization of diffusion,overcomes traditional dMRI artifacts, and is capable of more precise and detailedcharacterization of white matter fibers
Healthy Controls; gender aged match healthy	Diagnostic test: Siemens Biograph mMR (molecular MR); 5mCi of the radiotracer FDG administered intravenously as a bolus over 30s. After injection, emission data will be collected for 60 min,; Diagnostic test: fMRI; High-resolution T1-weighted structural image will be acquired using an MP2RAGE sequence. Subject will beasked to look at the cross hair on a screen andnot fixate on any one thought.; Diagnostic test: Diffusion Spectrum Imaging (DSI); DSI allows for more accurate characterization of diffusion,overcomes traditional dMRI artifacts, and is capable of more precise and detailedcharacterization of white matter fibers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intraindividual variation (ie IIV) in reaction times across the trials of the Attention Network Test (ANT)	Attention Network Test (ANT) is a cognitive reaction time test administered on the computer, where the subject indicates when they see a target on a screen.	Baseline
intraindividual variation (ie IIV) in reaction times across the trials of the Attention Network Test (ANT)	Attention Network Test (ANT) is a cognitive reaction time test administered on the computer, where the subject indicates when they see a target on a screen.	3 Months
intraindividual variation (ie IIV) in reaction times across the trials of the Attention Network Test (ANT)	Attention Network Test (ANT) is a cognitive reaction time test administered on the computer, where the subject indicates when they see a target on a screen.	6 Months
intraindividual variation (ie IIV) in reaction times across the trials of the Attention Network Test (ANT)	Attention Network Test (ANT) is a cognitive reaction time test administered on the computer, where the subject indicates when they see a target on a screen.	9 Months
intraindividual variation (ie IIV) in reaction times across the trials of the Attention Network Test (ANT)	Attention Network Test (ANT) is a cognitive reaction time test administered on the computer, where the subject indicates when they see a target on a screen.	12 Months

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Leigh Charvet, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): January 9, 2021
• Study Completion (Actual): January 9, 2021

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 24, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurocognitive Disorders; Multiple Sclerosis; Sclerosis; Cognition Disorders
• Other Study ID Numbers: 17-00238

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No