DreaMS - Validation Study 1

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: dreaMS App R2.1

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 450

Contacts and Locations

• Study Contact: Name: Johannes Lorscheider; Phone Number: +41615565796; Email: johannes.lorscheider@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland
    • Recruiting
    • MS Center, Department of Neurology University Hospital Basel
    • Contact: Johannes Lorscheider

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants of this study will be recruited from the outpatient department of the MS Center Basel at the University Hospital Basel.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Multiple Sclerosis (PwMS); PwMS will download the Healios+Me platform App which contains the dreaMS App and will follow the study schedule.	Device: dreaMS App R2.1; 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
Healthy Control Persons (HC); 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Research Center for Clinical Neuroimmunology and Neuroscience Basel
• Collaborators: Hoffmann-La Roche; Novartis Pharmaceuticals; University Hospital, Basel, Switzerland; University of Basel; Innosuisse - Swiss Innovation Agency; Healios AG
• Investigators: Study Director: Ludwig Kappos, Research Center for Clinical Neuroimmunology and Neuroscience Basel; Principal Investigator: Johannes Lorscheider, RC2NB and Department of Neurology, University Hospital of Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: July 23, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 17, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Digital Biomarker
• 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: DreaMS_2021VS1; SNCTP000004678 (Registry Identifier: Swiss National Clinical Trials Portal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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