Clinical trial NCT06501950: Measuring Silent Disease Progression in Multiple Sclerosis With a Multimodal Approach
Official title: Measuring Silent Disease Progression in Multiple Sclerosis With a Multimodal Approach
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Follow-Up
Observational study
PIRA
RRMS
PPMS
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2024-07-15
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with RRMS or PPMS that are currently treated with a monoclonal antibody.

Brief summary: This observational study wants to examine the disease progression independent of relapses in patients with Multiple Sclerosis (MS) that are treated with monoclonal antibodies. Participants will be clinically examined every 6 months and optionally receive a magnetic resonance imaging (MRI) every 12 months. The investigators will also take blood for blood biomarker tests with each clinical examination. Optionally, digital data can be continuously collected via smartphone and smartwatch.

With this information the study will compare the results from clinical, digital, radiological, and blood-based tests with the disease progression the participants report themselves. This study aims to investigate what percentage auf patients with MS under antibody treatment experience a slow progression of the disease.

Detailed description: The goal of this observational prospective, observational, multicenter proof of concept study is to identify silent disease progression in people with multiple sclerosis (MS) that are treated with monoclonal antibodies.

Progression independent of relapse activity (PIRA) refers to disability progression unrelated to relapses. Treatment with disease-modifying agent shifts the primary cause of disability towards PIRA, likely due to the prevention of relapses during therapy. In order to promptly identify these patients in the future, newer biomarkers are needed that can detect disease activity more sensitively. Digital health technologies (DHTs), such as connected wearables, offer the capability of continuously collecting real-life data. As they can capture movement patterns, sleep behavior, and cognition, DHTs can document silent disease progression in MS patients and have the potential to enhance our understanding of disease activity.

The goal of the 360 PMS (progressive Multiple Sclerosis) study is to evaluate various widely available smartwatch-derived digital metrics and blood-based analyses as well as imaging tools for monitoring silent disease activity in MS patients at two study centres. Patients with relapsing remitting or primary progressive MS that are treated with monoclonal antibodies and do not have an Expanded Disability Status Scale (EDSS) of more than 7,0 will be included in this study.

Clinical evaluations will be conducted every 6 months, as well as blood-based measurements that include serum neurofilament-light-chain (sNfL), glial fibrillary acidic protein (GFAP) and proteomic data. Data captured by smartwatches (Withings Scanwatch) include activity-related data (step count, minutes in certain intensity levels), basic cardiovascular measurements such as heart rate, and sleep-related data (total time asleep, sleep efficiency and quality etc.). Additionally, disease progression can be optionally evaluated by monitoring fine motor skills while typing on the smartphone by a smartphone application (Neurokeys).

The study will initially start at the core centre at the University Clinic Düsseldorf and plans to enrol further sites in the months following initiation. Further centers might not include optical coherence tomography (OCT) or MRI measurements. At the core facility additional examinations will be conducted: Structural MRI examinations will be conducted at baseline and in month 12 and 24. OCT measurements will examine retinal morphology and be conducted every 6 months.

The investigators will attempt to closely analyze MS patients under treatment with monoclonal antibodies with these methods. Data will be collected for a 24-month prospective period.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of RRMS or PPMS according to the 2017 McDonald criteria
* Current treatment with monoclonal antibodies (including Natalizumab, Ofatumumab, Ocrelizumab) according to SmPC
* EDSS ≤7.0

Exclusion Criteria:

* Patients with an acute MS relapse and/or a history of intravenous corticosteroid treatment within past six weeks.
* Any comorbidity resulting in an impairment to understand or successfully complete the study such as (but not restricted to) psychiatric comorbidities or dementia. Decision will be made at investigators discretion.
* Additional immunosuppression except of above mentioned monoclonal antibodies
* Pregnancy

Primary outcomes:
measure: Percentage of Progression independent from relapse (PIRA )at month 24
timeFrame: Baseline up to 24 months
Secondary outcomes:
measure: EDSS: Change From Baseline in Expanded Disability Status Scale (EDSS) Score
timeFrame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change From Baseline in World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Score
timeFrame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Paced Auditory Serial Addition Test
timeFrame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component 9-hole peg test
timeFrame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Timed 25-foot walk (T25FW)
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change in Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change From Baseline in Fatigue Severity Scale (FSS)
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change in blood-based serum filament lightchain (sNFL) levels
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change in blood-based glial fibrillary acidic protein(GFAP) levels
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change in proteomic signatures
timeFrame: Time Frame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Questionnaire about smartwatch usage (System Usability Score)
timeFrame: After 6 months and 24 months of use]
measure: Changes in fine motor skills composite as calculated by Neurokeys
timeFrame: Through study completion, up to two years
measure: Changes in cognition composite as calculated by Neurokeys
timeFrame: Through study completion, up to two years
measure: Wearing time of smartwatch (daily)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of activity parameter: step count
timeFrame: Continuously during the entire observation period
measure: Longitudinal development of activity parameter: approximate distance traveled (meter)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of activity parameter: duration of soft activity (seconds) defined by Withings
timeFrame: Through study completion, up to two years
measure: Longitudinal development of activity parameter: duration of moderate activity (seconds) defined by Withings
timeFrame: Continuously during the entire observation period (up to 24 months)
measure: Longitudinal development of activity parameter: duration of intense activity (seconds) defined by Withings
timeFrame: Through study completion, up to two years
measure: Longitudinal development of activity parameter: sum of all active time (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: time awake (seconds)
timeFrame: Continuously during the entire observation period (24 months)
measure: Longitudinal development of activity parameter: approximate calories burned
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: number of times user woke up
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: time to sleep (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: heart rate variability (ms)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: total time asleep (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: total time in bed (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: ratio of sleep/time in bed
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: time spent in bed before falling asleep (seconds
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: time awake after first falling asleep (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of sleep parameter: Withings Sleep score
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: maximal heartrate
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: minimum heartrate
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: time in light heartrate zone (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: time in moderate heartrate zone (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: time in intense heartrate zone (seconds)
timeFrame: Through study completion, up to two years
measure: Longitudinal development of cardiovascular parameter: time in maximal heartrate zone (seconds)
timeFrame: Through study completion, up to two years
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf, Department of Neurology
state: NRW
Study officials:
affiliation: Heinrich-Heine University, Duesseldorf
name: Marc Günter Pawlitzki, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kappos L, Wolinsky JS, Giovannoni G, Arnold DL, Wang Q, Bernasconi C, Model F, Koendgen H, Manfrini M, Belachew S, Hauser SL. Contribution of Relapse-Independent Progression vs Relapse-Associated Worsening to Overall Confirmed Disability Accumulation in Typical Relapsing Multiple Sclerosis in a Pooled Analysis of 2 Randomized Clinical Trials. JAMA Neurol. 2020 Sep 1;77(9):1132-1140. doi: 10.1001/jamaneurol.2020.1568.
citation: Masanneck L, Voth J, Huntemann N, Ozturk M, Schroeter CB, Ruck T, Meuth SG, Pawlitzki M. Introducing electronic monitoring of disease activity in patients with chronic inflammatory demyelinating polyneuropathy (EMDA CIDP): trial protocol of a proof of concept study. Neurol Res Pract. 2023 Aug 24;5(1):39. doi: 10.1186/s42466-023-00267-3.