DreaMS - Validation Study 1

Study Overview
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Brief Summary
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Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) causing focal lesions of demyelination and diffuse neurodegeneration in the grey and white matter of the brain and spinal cord, leading to physical and cognitive disability. The scientific community and patients are in need for new and more reliable biomarkers, especially biomarkers of disease progression in order to adapt therapeutic approaches on an individual level. Digital biomarkers have the potential to fill this gap allowing for quasi-continuous measures that might be more informative than episodically collected conventional data concerning the impact of the disease on activities of daily living. Using app-based challenges, continuous monitoring and surveys the Investigators aim to obtain data that can be used as digital biomarkers (DB). These digital biomarkers will provide more granular and precise assessments, thus complementing traditional diagnostic measures and techniques. After a first feasibility study (ClinicalTrials.gov: NCT04413032) a number of digital biomarkers have been identified as reliable, reproducible and meaningful to PwMS and are therefore being validated in a bigger cohort of PwMS with a longer follow-up within this validation study 1. Those digital biomarkers will be compared to state-of-the-Art clinical, imaging and body fluid assessment.

Detailed Description
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Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) causing focal lesions of demyelination and diffuse neurodegeneration in the grey and white matter of the brain and spinal cord, leading to physical and cognitive disability. Currently there is a limited number of relevant biomarkers available in persons with MS (PwMS), such as clinical, imaging or biological measures. Patient history and neurologic examination in combination with magnetic resonance imaging (MRI), evoked potentials and analysis of serum and cerebrospinal fluid (CSF) are the gold standard of diagnosis and mainly patient history, neurologic examination and MRI are used for patient monitoring. However, their prognostic value on a patient level is still very limited. Therefore, the scientific community and patients are in need for new and more reliable biomarkers, especially biomarkers of disease progression in order to adapt therapeutic approaches on an individual level. Digital biomarkers have the potential to fill this gap allowing for quasi-continuous measures that might be more informative than episodically collected conventional data concerning the impact of the disease on activities of daily living. The Investigators have developed the Healios+Me platform App which contains the dreaMS App and serves as a data collection, communication and management platform using data collected through the patients' mobile devices (smartphone and wearables). Using the dreaMS app-based challenges, continuous monitoring and surveys the Investigators aim to obtain data that can be used as digital biomarkers (DB). These digital biomarkers will provide more granular and precise assessments, thus complementing traditional diagnostic measures and techniques. After a first feasibility study (ClinicalTrials.gov: NCT04413032) a number of digital biomarkers have been identified as reliable, reproducible and meaningful to PwMS and are therefore being validated in a bigger cohort of PwMS with a longer follow-up within this validation study 1. Those digital biomarkers will be compared to state-of-the-Art clinical, imaging and body fluid assessment.

Official Title
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DreaMS - Development of Digital Biomarkers in Multiple Sclerosis - Validation Study 1

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Device: dreaMS App R2.1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 Diagnosed with MS according to the revised McDonald criteria 2017, all clinical forms inclusive (CIS, RRMS, SPMS, PPMS), for PwMS only In possession of a Healios+Me App compatible smartphone (iOS/Android) Corrected close visual acuity of ≥0.5 Hand motor skills sufficient for using a smartphone Ability to follow the study procedures Informed Consent as documented by signature Exclusion Criteria: Being diagnosed with MS or other disease affecting neurological and cognitive functions, for HC only Other clinically significant concomitant disease states (e.g., renal failure, severe hepatic dysfunction, severe/unstable cardiovascular disease, progressive cancer, etc.) Known or suspected non-compliance, drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Multiple Sclerosis (PwMS)<br>PwMS will download the Healios+Me platform App which contains the dreaMS App and will follow the study schedule. | Device: dreaMS App R2.1<br>* The Healios+Me platform App which contains the dreaMS App will be downloaded by all participants and all participants (PwMS and HC) will follow the same schedule<br>|
| Healthy Control Persons (HC)<br>HC will download the Healios+Me platform App which contains the dreaMS App and will follow the same study schedule as PwMS. | Device: dreaMS App R2.1<br>* The Healios+Me platform App which contains the dreaMS App will be downloaded by all participants and all participants (PwMS and HC) will follow the same schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of the digital features with the respective measurements of the clinical reference tests | Spearman correlation coefficients higher than 0.4 (lower bound of 95% confidence interval) are considered relevant. All scheduled pairs of measurements collected during the study will be used. As the yearly observations of a patient are not independent, standard conﬁdence intervals cannot be used. Therefore, a bootstrap approach will be used to determine a 95% conﬁdence interval for the Spearman correlations (where data will be resampled on the patient level). | Baseline to last visit (year two) | 
| The ability of measurements of the changes in the digital biomarkers over the two-year follow-up to predict worsening in the clinical reference test over the same period expressed as binary variables | The change of the digital biomarker over two years allows to distinguish patients experiencing a relevant worsening in the corresponding reference test over the same period from those who do not with an area under the receiver operating characteristic curve (AUC) larger than 0.6 (lower bound of 95% confidence interval). | Measurements at baseline and after two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Digital Biomarker