Clinical trial NCT06461481: Strategies for Adaptive Follow-up and Evaluation - Guiding Use of Indicators for De-Escalation in Multiple Sclerosis
Official title: Strategies for Adaptive Follow-up and Evaluation - Guiding Use of Indicators for De-Escalation in Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis, Follow-Up
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2024-06-17
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 150 MS patients after treatment de-escalation/discontinuation

Brief summary: The study will attempt to closely analyze Multiple Sclerosis (MS) patients after de-escalating or discontinuation of immunotherapy using clinical monitoring as well as digital and serological biomarkers in order to detect clinical progression or disease activity. As this is an observational study, it aims to closely follow-up on patients where the clinical decision to de-escalate or end treatment has been independently made. Specifically, we want to find out to what extent patients will show increased disease activity after de-escalation/discontinuation from high-efficacy treatment (HET) and which measurement method (clinical, digital, serological) retrospectively reflects the disease activity most closely or detects it most sensitively.

Detailed description: Due to the increasing scientific efforts in recent years, a variety of HET are now available for patients with MS. In addition to long-term clinical assessment, monitoring by means of magnetic resonance imaging (MRI) has also become increasingly established. No evidence of disease activity under appropriate immunotherapy has thus been defined in a wide variety of concepts using clinical and MRI parameters. These medical achievements have positively influenced the natural course of MS, especially by significantly reducing the relapse activity. In contrast, however, the risk of potential complications under long-term immunotherapy should not be underestimated. This concerns in particular infection risks but also an increased malignancy risk for various, mostly highly effective immunotherapies.

Therefore, the question increasingly arises in clinical practice as to what extent HET should be continued or should be de-escalated in case of long-term disease course. As patients and doctors take clinical decision to de-escalate their therapies, often after many years of little or even no disease activity, the central question of how to best monitor patients subsequently remains. Digital smartwatch-based measurements or app-based regular assessments could add high-frequency real-world data to the picture and thus improve the understanding of individual disease courses. Additionally, novel serological markers to detect neuronal damage are becoming more widely available. Consequently, this study aims to evaluate different digital measurements and blood-based analyses to monitor disease activity in MS patients, which have independently with their treating physicians decided to discontinue or de-escalate their disease-modifying treatment of MS.

Data captured by the used smartwatches (Withings Scanwatch) includes 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.). Blood-based measurements include serum neurofilament-light-chain (sNfL), glial fibrillary acidic protein (GFAP) and proteomic data. The investigators will attempt to closely analyze MS patients after de-escalating or discontinuation of immunotherapy using digital and serological biomarkers in order to detect possible increased disease activity. In addition to clinical assessment, structural MRI examinations will be optionally conducted in patients from core center at baseline and in month 12 and 24. Measurement parameters from clinical MRI examinations (lesion load) are also taken into account from the other study centers. In addition to that, patients from core center will undergo an Optical coherence tomography (OCT) measurement. OCT is a non-invasive, interferometric method that allows for detailed visualization of retinal morphology and is known to reveal abnormalities in various central nervous system (CNS) disorders. Data will be collected for a 24-month prospective period.

Eligibility criteria: Inclusion Criteria:

* Diagnosed RRMS according to 2017 revised McDonald criteria 12
* De-escalation of high-efficacy treatment or discontinuation of lower efficacy disease modifying therapy (DMT)
* Own a smartphone (only core centre) EDSS \<7.0
* able to handle a smartphone (only core centre)

Exclusion Criteria:

* Patients with an acute MS relapse and/or a history of intravenous corticosteroid treatment or immunoadsorption 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.
* Diagnosis of primary or secondary progressive MS

Primary outcomes:
measure: Percentage of disease activity, measured by loss of NEDA 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: 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: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5)
measure: Change From Baseline in Fatigue Severity Scale (FSS)
timeFrame: Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months)
measure: Change in Blood analysis (levels of sNfl, GFAP, serum proteomics)
timeFrame: Time frame: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5)
measure: Questionnaire about smartwatch usage (System Usability Score)
timeFrame: After 6 months and 24 months of use
measure: Wearing time of smartwatch (daily)
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: step count
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: approximate distance traveled (meter)
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: duration of soft activity (seconds) defined by Withings
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: duration of moderate activity (seconds) defined by Withings
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: duration of intense activity (seconds) defined by Withings
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: sum of all active time (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: time awake (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of activity parameter: approximate calories burned
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: number of times user woke up
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: time to sleep (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: heart rate variability (ms)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: total time asleep (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: total time in bed (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: ratio of sleep/time in bed
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: time spent in bed before falling asleep (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: time awake after first falling asleep (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of sleep parameter: Withings Sleep score
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: average heartrate
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: maximal heartrate
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: minimum heartrate
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: time in light heartrate zone (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: time in moderate heartrate zone (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: time in intense heartrate zone (seconds)
timeFrame: during the entire observation period
measure: Longitudinal development of cardiovascular parameter: time in maximal heartrate zone (seconds)
timeFrame: during the entire observation period
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: Heinrich-Heine University, Duesseldorf
Study officials:
affiliation: Heinrich-Heine University, Duesseldorf
name: Marc Günter Pawlitzki, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: