Strategies for Adaptive Follow-up and Evaluation - Guiding Use of Indicators for De-Escalation in Multiple Sclerosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Percentage of disease activity, measured by loss of NEDA at month 24
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
结局指标
主要结局
Percentage of disease activity, measured by loss of NEDA at month 24
时间窗: Baseline up to 24 months
According to NEDA-3 (Giovannoni et al., 2015) indicated by relapse, EDSS or cerebral magnetic resonance imaging (MRI) activity.
次要结局
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Timed 25-foot walk (T25FW)(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Change in Pittsburgh Sleep Quality Index (PSQI)(Time frame: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5))
- Wearing time of smartwatch (daily)(during the entire observation period)
- EDSS: Change From Baseline in Expanded Disability Status Scale (EDSS) Score(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Change in Blood analysis (levels of sNfl, GFAP, serum proteomics)(Time frame: Screening + Baseline (V1), After 6 months (V2), After 12 months (V3), After 18 months (V4), After 24 months (V5))
- Longitudinal development of sleep parameter: time awake (seconds)(during the entire observation period)
- Longitudinal development of sleep parameter: total time in bed (seconds)(during the entire observation period)
- Longitudinal development of sleep parameter: Withings Sleep score(during the entire observation period)
- Change From Baseline in World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Score(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component Paced Auditory Serial Addition Test(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score - Component 9-hole peg test(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Change From Baseline in Fatigue Severity Scale (FSS)(Baseline up to 24 months (after 6 months, 12 months, 18 months, 24 months))
- Longitudinal development of sleep parameter: heart rate variability (ms)(during the entire observation period)
- Longitudinal development of sleep parameter: ratio of sleep/time in bed(during the entire observation period)
- Questionnaire about smartwatch usage (System Usability Score)(After 6 months and 24 months of use)
- Longitudinal development of activity parameter: step count(during the entire observation period)
- Longitudinal development of activity parameter: duration of intense activity (seconds) defined by Withings(during the entire observation period)
- Longitudinal development of sleep parameter: number of times user woke up(during the entire observation period)
- Longitudinal development of activity parameter: approximate distance traveled (meter)(during the entire observation period)
- Longitudinal development of activity parameter: duration of soft activity (seconds) defined by Withings(during the entire observation period)
- Longitudinal development of activity parameter: duration of moderate activity (seconds) defined by Withings(during the entire observation period)
- Longitudinal development of activity parameter: sum of all active time (seconds)(during the entire observation period)
- Longitudinal development of activity parameter: approximate calories burned(during the entire observation period)
- Longitudinal development of sleep parameter: time to sleep (seconds)(during the entire observation period)
- Longitudinal development of sleep parameter: total time asleep (seconds)(during the entire observation period)
- Longitudinal development of cardiovascular parameter: time in maximal heartrate zone (seconds)(during the entire observation period)
- Longitudinal development of sleep parameter: time spent in bed before falling asleep (seconds)(during the entire observation period)
- Longitudinal development of cardiovascular parameter: time in light heartrate zone (seconds)(during the entire observation period)
- Longitudinal development of cardiovascular parameter: time in moderate heartrate zone (seconds)(during the entire observation period)
- Longitudinal development of cardiovascular parameter: time in intense heartrate zone (seconds)(during the entire observation period)
- Longitudinal development of sleep parameter: time awake after first falling asleep (seconds)(during the entire observation period)
- Longitudinal development of cardiovascular parameter: average heartrate(during the entire observation period)
- Longitudinal development of cardiovascular parameter: maximal heartrate(during the entire observation period)
- Longitudinal development of cardiovascular parameter: minimum heartrate(during the entire observation period)
研究者
Dr. med. Marc Günter Pawlitzki
Study Coordinator
Heinrich-Heine University, Duesseldorf