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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Custom study version of icompanion app


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Main arm<br>Use of icompanion through will all assessments are performed | Other: Custom study version of icompanion app<br>* 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.<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognition