Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands

Обзор

The goal of this clinical trial is to investigate the feasibility if a remotely administered smartphone app can increase the volume and intensity of physical activity in daily life in patients with isolated Rapid Eye Movement (REM) sleep behaviour disorder over a long period of time (24 months). Participants will be tasked to achieve an incremental increase of daily steps (volume) and amount of minutes exercised at a certain heart rate (intensity) with respect to their own baseline level. Motivation with regards to physical activity will entirely be communicated through the study specific Slow Speed smartphone app. Primary outcomes will be compliance expressed as longitudinal change in digital measures of physical activity (step count) measured using a Fitbit smartwatch. Exploratory outcomes entail retention rate, completeness of remote digital biomarker assessments, digital prodromal motor and non-motor features of PD, blood biomarkers and brain imaging markers. Using these biomarkers, we aim to develop a composite score (prodromal load score) to estimate the total prodromal load. An international exercise study with fellow researchers in the United States and United Kingdom are currently in preparation (Slow-SPEED). Our intention is to analyse overlapping outcomes combined where possible through a meta-analysis plan, to obtain insight on (determinants of) heterogeneity in compliance and possible efficacy across subgroups

Подробное описание

Rationale: Parkinson's Disease (PD) is the fastest growing neurodegenerative disease. Exercise beneficially effects motor symptoms and neuroplasticity in people with PD. However, disease-slowing interventions have been ineffective in clinically manifest PD, when pathology is already advanced, but could succeed in prodromal PD, when pathology is limited. People with an isolated Rapid Eye Movement (REM) sleep Behaviour Disorder (iRBD) have a high risk to develop clinically manifest PD or a related neurodegenerative disease and are therefore considered to have probable prodromal PD. This study will take an important step forward by studying the feasibility and preliminary efficacy of long-term physical activity on prodromal symptoms and disease progression in people with probable prodromal PD using a newly developed, fully remote smartphone-based app. The app is inspired by the app used in the STEPWISE trial (NCT04848077).

Objective: The goal of this clinical trial is to investigate whether a smartphone app can increase the volume and intensity of physical activity in daily life in patients with iRBD at risk of developing PD for a long period of time (24 months). The secondary aim is the potential group effect on physical fitness, digital prodromal motor- and non-motor symptoms. Thirdly, we investigate whether the intervention, prodromal motor- and non-motor symptoms can be assessed remotely in a digital, decentralized fashion. Fourthly, we aim to investigate the effect on imaging- and fluid biomarkers to identify markers for prodromal progression. Using these biomarkers, we aim to develop a composite score (prodromal load score) to estimate the total prodromal load.

The anticipated fluid biomarkers outcomes are subject to potential alterations in the event of the development and implementation of novel techniques and/or biomarkers during the course of this study.

Study design: Double-blind randomized controlled trial

Study population: A total of 110 Dutch patients with iRBD (ICSD-3 criteria) aged 50 years and older, who are in possession of a suitable smartphone without mobility hampering conditions and absence of cognitive impairment which impedes usage of a smartphone will be recruited

Intervention: Participants will be randomized to a group and will be motivated to increase the volume and intensity of physical activity based on their own baseline level. The groups differ in the amount of physical activity that they are tasked to achieve.

Вмешательства

• Поведенческое Increase of physical activity volume and intensity with the use of a motivational smartphone application
  A motivational smartphone application will be available for all participants using their own smartphone: the Slow-SPEED app. The Slow-SPEED app will motivate participants to increase the volume and intensity of their physical activity in daily life over a long period of time (2 years) based on their own baseline levels. Different treatment arms will receive different physical activity goals. The app offers participants feedback and support, that will stimulate them to reach their individual phys

Первичные конечные точки

• Mean change in step count per day [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]

Вторичные конечные точки (12)

• Change in moderate to vigorous physical activity (MVPA) per day [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Change in resting heart rate (physical fitness) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Change in heart rate variability (physical fitness) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Change in blood pressure (physical fitness) [Срок оценки: Week 0 (baseline) and week 104 (follow-up)]
• Change in VO2max (physical fitness) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Change in heart rate variability (autonomic function) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Change in orthostatic blood pressure (autonomic function) [Срок оценки: Week 0 (baseline) and week 104 (follow-up)]
• Change in anxiety and depression (HADS) [Срок оценки: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)]
• Change in cognition (MoCA) [Срок оценки: Week 0 (baseline), week 104 (follow-up)]
• Mean change in light sleep (sleep stage) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Mean change in deep sleep (sleep stage) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]
• Mean change in REM sleep (sleep stage) [Срок оценки: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)]

Критерии участия

Критерии включения

• previously diagnosed with iRBD meeting the following criteria according to the International Classification of Sleep Disorders (ICSD-3)
• able to understand the Dutch language
• being able to walk independently inside the home without the use of a walking aid
• Not in a high physical activity range during the 4-week eligibility and baseline period
• in possession of a suitable smartphone compatible with the Slow-SPEED app, the Fitbit app and the Roche PD Research Mobile application.

Критерии исключения

• clinically diagnosed or self-reported diagnosis neurodegenerative disease;
• self-reported weekly falls in the previous 3 months;
• dexterity problems or cognitive impairments hampering smartphone use;
• if they do not wish to be informed about an increased risk of developing diseases associated with iRBD
• if individual is not community-dwelling

Exclusion criteria for MRI only:

• history of epilepsy, structural brain abnormalities (i.e. stroke, traumatic defects, large arachnoid cysts) or brain surgery
• claustrophobia
• implanted electrical devices (i.e. pacemaker, deep-brain stimulator (DBS), neurostimulator)
• metal implants (such as prosthetics, ossicle prosthesis, metal plates or other non-removable metal part) or metal splinters
• pregnancy
• fear for incidental finding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Профилактика

Центры проведения

Нидерланды · 1 центр

• Radboud University Medical Center — Nijmegen

Публикации

• Oosterhof TH, Mitchell E, Ascherio A, Aslibekyan S, Azoidou V, Beasley K, Ben-Shlomo Y, Bunnik E, Carroll C, Chahine L, Corcos D, Janssen Daalen JM, van Dijk KD, Dijkstra BW, Dommershuijsen L, Dorsey R, Evers LJW, Helmich RC, Johansson M, Norcliffe-Kaufmann L, Keavney J, Klein C, Kmiecik MJ, Kustermann T, Macklin EA, Marek K, Meles SK, Overeem S, Philpott CM, Pijpers A, Postuma RB, Rowbotham HM, S PMID 42448717
• Tolosa E, Poewe W, Noyce AJ, Svenningsson P, Mahlknecht P, Marti MJ. Towards biomarker-based diagnosis of Parkinson disease. Nat Rev Neurol. 2026 Mar;22(3):139-151. doi: 10.1038/s41582-026-01185-z. Epub 2026 Feb 13. PMID 41688680

Идентификаторы

NCT: NCT06193252 · NL84072.091.23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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