CogMS - A Real-world Study Into Cognitive Impairment in People With Multiple Sclerosis

The present study will investigate the correlation between objective and subjective cognition in multiple sclerosis. The study will also investigate the impact of covariates such as fatigue and depression, the relationship with the Expanded Disability Status Scale (EDSS) and brain volumetrics as measured on magnetic resonance imaging (MRI). Additionally, the study will provide insights into patients' experiences with cognition, and the usability of the used objective cognitive assessments.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Custom study version of icompanion app

Detailed Description

Cognitive impairment is a significant burden that affects 43 to 70% of persons with multiple sclerosis (pwMS) 1. Cognitive problems have been observed in the earliest stages of multiple sclerosis (MS) and multiple studies have provided evidence for the predictive value of early cognitive impairment for future disease progression 2-6. However, cognitive function is not often discussed with pwMS or routinely assessed by healthcare providers (HCPs) leading to sub-optimal treatment of cognitive problems in MS 7. Furthermore, cognitive dysfunction that can be reliably detected by objective measures is poorly recognized by pwMS, resulting in a disconnect between objective and subjective measures of cognitive function 8-10.

The present study will investigate the correlation between what cognitive problems people with MS perceive and what objective cognitive testing actually shows. This study will also provide insights about the presence of this disconnect in different strata of the Expanded Disability Status Scale (EDSS) 11, and the relationship with possible confounders (MS symptoms, fatigue, etc.) and brain volumetrics as measured on magnetic resonance imaging (MRI).

Study Design:

CogMS is an observational, cross-sectional, remote, real-world study of cognitive function in patients with multiple sclerosis. We will investigate the correlation between subjective and objective patient self-evaluations of cognitive function while also investigating the prevalence of objective cognitive impairment in different EDSS strata of pwMS. MS patients will be stratified by EDSS to evaluate the correlation between objective and subjective cognition in three different EDSS strata (EDSS 0 - 2; 2.5 - 3.5; 4.0 - 5.5) and the occurrence of objective cognitive dysfunction in these EDSS stages of MS.

All data will be captured using the icompanion app in a remote, non-clinical setting (i.e., patient's home) within three weeks of patient onboarding. In the icompanion app, patients will be asked to perform the icognition cognitive test battery together with patient-reported outcomes (PROs) for subjective cognition, MS symptoms, prEDSS, depression and fatigue. If available, a recent (max. 6 months) MRI scan will be provided from which volumetric measurements can be calculated using icometrix' icobrain software.

Finally, patients will be asked to answer questions on their experiences with cognition since diagnosis, their preferences and opinions about cognition as a treatment goal, and the usability of the icognition battery, and the preference compared to paper-based neuropsychological tests.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

• Study Contact: Name: Lars Costers, PhD; Phone Number: +3216 36 90 00; Email: lars.costers@icometrix.com
• Study Contact Backup: Name: Annabel Descamps; Phone Number: +3216 36 90 00; Email: annabel.descamps@icometrix.com

Study Locations

• Belgium
  • Antwerpen, Belgium, 2018
    • GZA Antwerpen
    • Contact: Frederik Debruyne, Dr.
  • Bonheiden, Belgium, 2820
    • Imelda Ziekenhuis
    • Contact: Maarten Dewil, Dr.
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge
    • Contact: Melissa Cambron, Dr.
  • Jette, Belgium, 1090
    • UZ Brussel
    • Contact: Guy Nagels, Dr.; Email: guy.nagels@uzbrussel.be
• Germany
  • Greifswald, Germany, 17489
    • University of Greifswald
    • Contact: Matthias Grothe, Dr.
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth
    • Fort Collins, Colorado, United States, 80528
      • Brain Health Center of the Rockies
      • Contact: Augusto Miravalle, Dr.
  • New York
    • Buffalo, New York, United States, 14226
      • Dent Neurologic Institute
      • Contact: Bennett Myers, Dr.
  • Ohio
    • Columbus, Ohio, United States, 43235
      • The Boster Center for Multiple Sclerosis
  • Texas
    • Dallas, Texas, United States, 75206
      • Texas Neurology
      • Contact: Arun Nagaraj, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

300 CIS/RRMS patients, aged 18 to 65 (inclusive), with a maximum disease duration of 15 years.

Description

Inclusion Criteria:

• Providing a signed informed consent
• Aged between 18 and 65 years old
• MS diagnosis (CIS, RRMS)
• Absence of hand function problems which limit the use of a device like a smartphone
• No history of relapse with onset 30 days prior to start of study
• No other major neurological or psychiatric disorders
• No history of cognitive rehabilitation treatment

Exclusion Criteria:

• Disease duration longer than 15 years
• Patients with established cognitive disorders other than MS
• Drug and/or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Main arm; Use of icompanion through will all assessments are performed	Other: Custom study version of icompanion app; Patients complete patient-reported outcomes on cognition and covariates, as well as objective cognitive tests through a version of icompanion app customized specifically for this study. Patients complete all assessments remotely in an at-home situation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuro-QoL cognitive	The Neuro-QoL (Quality of Life in Neurological Disorders) is a patient-reported outcome for subjective cognitive problems Minimum and maximum values: 8-40 (t-score: 17.3-64.2). High scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
icognition Symbol test score	The icognition Symbol test is a smartphone-based symbol substitution test for information processing speed Minimum and maximum values: to be determined by a separate study which is being finalised High scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
icognition Dot test score	The icognition Dot test score is a smartphone-based test for visual working memory Minimum and maximum values: to be determined by a separate study which is being finalised High scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
icognition Digit test score	The icognition Digit test score is a smartphone-based test for working memory Minimum and maximum values: to be determined by a separate study which is being finalised High scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prEDSS	is a patient-reported outcome (PRO) version of the Expanded Disability Status Scale (EDSS), the current golden standard method for assessing disability (progression) in MS. Minimum and maximum values: 0-10 Low scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
Neuro-QoL fatigue	Neuro-QoL Fatigue is a patient-reported outcome for fatigue Minimum and maximum values: 8-40 (t-score: 29.5-74.1). Low scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
Beck's depression inventory	The BDI is a 21-question multiple-choice self-report psychometric tests for measuring the severity of depression. Minimum and maximum values: 0-63. Low scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)
MRI volumetric variables	icobrain volumetric MRI measurements: whole brain volume and atrophy, grey matter volume and atrophy, lesion load, total lesion volume, volume of new lesions, volume of enlarging lesions, volume of shrinking lesions, lesion volume and volume changes assessed locally (i.e. juxtacortical, periventricular, deep white matter, infratentorial)	at time of enrolment in study (in case MRI of <6months is available)
System usability score (cognitive smartphone-based tests)	Usability questionnaire	Single cross-sectional time-point (max 2 months after signing ICF)
Preference icognition vs. paper-based assessments	Likert scale [0-5]	Single cross-sectional time-point (max 2 months after signing ICF)
SymptoMScreen	Questionnaire assessing the severity of the twelve most common MS Symptoms Minimum and maximum values: 0-6 Low scores indicate better (desirable) self-reported health.	Single cross-sectional time-point (max 2 months after signing ICF)

Collaborators and Investigators

• Sponsor: icometrix
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Guy Nagels, Prof., UZ Brussel - icometrix

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2023
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): December 6, 2023

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Cognition
• 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; Cognition Disorders; Multiple Sclerosis; Sclerosis; Cognitive Dysfunction
• Other Study ID Numbers: ICO-S-001

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: No
• product manufactured in and exported from the U.S.: No