Parkinson DiseaseSlow-SPEED-NLNCT06193252
Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands
A study testing Increase of physical activity volume and intensity with the use of a motivational smartphone application in people with Parkinson Disease and Prodromal Stage, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Parkinson Disease, Prodromal Stage, Neurodegenerative Diseases
- What is being tested?
- Increase of physical activity volume and intensity with the use of a motivational smartphone application
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Jan 2024to 1 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
- history of epilepsy, structural brain abnormalities (i.e. stroke, traumatic defects, large arachnoid cysts) or brain surgery
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6525 GA
Thomas Oosterhof, MSc, +31631647857, slow-speed@radboudumc.nl
About this study
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
Read the detailed description
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.
- Conditions
- Parkinson Disease, Prodromal Stage, Neurodegenerative Diseases, Parkinsonian Disorders, REM Sleep Behavior Disorder, Basal Ganglia Diseases
- Being tested
- Increase of physical activity volume and intensity with the use of a motivational smartphone application
- Keywords
- Physical Activity, Prevention, Remote, Mobile Health (mHealth), Feasibility, Exercise, Digital biomarker, Blood, Imaging, MRI, Motivational application, Walking, Parkinson Disease, Prodromal
- Medical subject headings
- Parkinson Disease, Prodromal Symptoms, Neurodegenerative Diseases, Parkinsonian Disorders, REM Sleep Behavior Disorder, Basal Ganglia Diseases, Central Nervous System Diseases, Synucleinopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Increase of physical activity volume and intensity with the use of a motivational smartphone applicationBehavioural
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 physical activity goal (i.e. incremental relative increase of step count and minutes exerting ≥ 64% of maximum heart rate reflecting MVPA relative to baseline level.).
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Large proportional increase in step count and minutes exerting moderate to vigorous physical activity (MVPA) relative to baseline level. Receives: Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone application |
| Active control | Active comparator | Small proportional increase in step count and minute exerting moderate to vigorous physical activity (MVPA) relative to baseline level. Receives: Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone application |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in step count per day
Mean change in step count per day as measured continuously with a smartwatch. Mean steps per day will be calculated from 4-week periods. Higher positive change in step count indicate more volume of physical activity.
Measured: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
Secondary outcomes (44)
Change in moderate to vigorous physical activity (MVPA) per day
Change in number of minutes exerting (minimally) ≥ 64% of maximum heart rate, reflecting moderate intense physical activity, measured continuously using a smartwatch. Mean minutes per day will be calculated from 4-week periods. Higher positive change in minutes of MVPA indicate more aerobic physical activity.
Measured: 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)
Change in resting heart rate per day as measured continuously with a smartwatch. Mean resting heart rate per day will be calculated from 4-week periods. Higher negative change (i.e. lower resting heart rate) indicate better function.
Measured: 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)
Change in heart rate variability in Root Mean Square of Successive Differences (RMSSD) measured every 5 minutes with a smartwatch. Mean RMSSD per day will be calculated from 4-week periods. Higher positive change in RMSSD indicate better function.
Measured: 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)
Change from baseline (week 0) blood pressure in mmHg assessed by a sphygmomanometer at follow-up (week 104). Lower scores indicate better function.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in VO2max (physical fitness)
Change in VO2max in ml/kg/min measured per day with a smartwatch. Mean VO2max per day will be calculated from 4-week periods. Higher positive change in VO2max indicate better function.
Measured: 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)
Mean change in heart rate variability in Root Mean Square of Successive Differences (RMSSD) measured every 5 minutes with a smartwatch. Mean RMSSD per day will be calculated from 4-week periods. Higher positive change in RMSSD indicate better function.
Measured: 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)
Change in baseline (week 0) difference between supine and standing blood pressure measured with a sphygmomanometer to follow-up (week 104). Higher change indicate more autonomic dysfunction.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in anxiety and depression (HADS)
Change from baseline (week 0) on the Hospital Anxiety and Depression Scale (HADS) at week 52 (1 year) and week 104 (follow-up). Range 0-42. Higher scores indicate worse function.
Measured: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
Change in cognition (MoCA)
Change from baseline (week 0) on the Montreal Cognitive Assessment (MoCA) at week 104 (follow-up). Range 0-30. Higher scores indicate better function.
Measured: Week 0 (baseline), week 104 (follow-up)
Mean change in light sleep (sleep stage)
Mean change in light sleep stage measured continuously with a smartwatch. Mean duration of light sleep per day will be calculated from 4-week periods. Higher positive change indicate more light sleep.
Measured: 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)
Mean change in deep sleep stage measured continuously with a smartwatch. Mean duration of deep sleep per day will be calculated from 4-week periods. Higher positive change indicate more deep sleep.
Measured: 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)
Mean change in rapid eye movement (REM) sleep stage measured continuously with a smartwatch. Mean duration of REM sleep per day will be calculated from 4-week periods. Higher positive change indicate more REM sleep.
Measured: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
Change in self-reported sleep quality (PSQI)
Change from baseline (week 0) on the Pittsburgh Sleep Quality Index (PSQI) at week 52 (1 year) and week 104 (follow-up). Range 0-21. Higher scores indicate worse sleep quality.
Measured: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
Change in olfaction (UPSIT)
Change from baseline (week 0) on the University of Pennsylvania Smell Identification Test (UPSIT) at week 104 (follow-up). Range 0-40. Higher scores indicate better function.
Measured: Week 0 (baseline), week 104 (follow-up)
Change in motor symptoms (Roche PD Research mobile application)
Change in motor symptoms measured digitally with the smartphone using the Roche PD Research mobile application. Higher scores indicate worse function.
Measured: Week 0 (baseline), week 6, week 12, week 18, week 24, week 30, week 36, week 42, week 48, week 54, week 60, week 66, week 72, week 78, week 84, week 90, week 96, week 102
Change in metabolism (blood based biomarkers)
Change from baseline (week 0) on glucose and HbA1c at follow-up (week 104). Optional at week 26, week 52 and week 78. Lower scores indicate better metabolism.
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in inflammation (blood based biomarkers)
Change from baseline (week 0) on Tumor Necrosis Factor-α, Interleukin-6 (IL-6), IL-18, IGF-1, clusterin, Il-10, PGC-α (irisin) at follow-up (week 104). Optional at week 26, week 52 and week 78. Lower inflammatory markers indicate less inflammation. Higher anti-inflammatory markers indicate less inflammation.
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in growth factors (blood based biomarkers)
Change from baseline (week 0) on brain-derived neurotrophic factor (BDNF), Glial cell line-derived neurotrophic factor (GDNF), Platelet-derived growth factor (PDGF), Growth/differentiation factor 15 (GDF15) and Epidermal growth factor (EGF) at follow-up (week 104). Optional at week 26, week 52 and week 78. Higher growth factors indicate better function.
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in ageing mechanism (blood based biomarkers)
Change from baseline (week 0) on klotho at follow-up (week 104). Optional at week 26, week 52 and week 78. High ageing marker indicate better function (i.e. less aging)
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in pathological protein (blood based biomarkers)
Change from baseline (week 0) on α-synuclein at follow-up (week 104). Optional at week 26, week 52 and week 78. Low pathological protein indicate better function (i.e. less pathological process).
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in neurodegeneration (blood based biomarkers)
Change from baseline (week 0) on Neurofilament light (NfL) at follow-up (week 104). Optional at week 26, week 52 and week 78. Lower neurodegeneration markers indicate less neurodegeneration.
Measured: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in brain volume (imaging biomarkers)
Change from baseline (week 0) on T1 Voxel-Based-Morphometry (VBM) at follow-up (week 104). Higher scores indicate higher volume.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in white matter hyperintensities (imaging biomarkers)
Change from baseline (week 0) on FLAIR at follow-up (week 104). Higher scores indicate worse status.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in basal ganglia; cortex [1] (imaging biomarkers)
Change from baseline (week 0) on resting-state functional MRI (Rs-fMRI) at follow-up (week 104). Higher scores indicate better functional connectivity.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in basal ganglia; cortex [2] (imaging biomarkers)
Change from baseline (week 0) on task-based functional MRI at follow-up (week 104). Higher scores indicate better functional connectivity.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [1] (imaging biomarkers)
Change from baseline (week 0) on diffusion tensor imaging (DTI) at follow-up (week 104). Higher scores indicate better tissue integrity.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [2] (imaging biomarkers)
Change from baseline (week 0) on Quantitative Susceptibility Mapping (QSM) at follow-up (week 104). Higher scores indicate more iron loading.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [3]; locus coeruleus (imaging biomarkers)
Change from baseline (week 0) on neuromelanin at follow-up (week 104). Higher scores indicate better tissue integrity.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in instrumental activities of daily living (ADL) (functional status)
Change from baseline (week 0) on Lawton instrumental ADL (iADL) scale at week 52 (1 year) and 104 (follow-up). Range 0-14. Higher score indicate better function.
Measured: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
Change in WHOQoL-BREF (quality of life)
Change from baseline (week 0) on World Health Organization Quality of Life Questionnaire - BREF (WHOQoL-BREF) scale at week 52 (1 year) and 104 (follow-up). Range 0-100. Higher score indicate better quality of life.
Measured: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
Change in Research and Development (RAND-36)/Short Form health survey (SF-36) (quality of life)
Change from baseline (week 0) on RAND-36/SF-36 scale at week 52 (1 year) and 104 (follow-up). Range 0-100. Higher score indicate better quality of life.
Measured: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
System Usability (SUS)
Usability of the Slow-SPEED-NL application assessed by the Dutch version of the System Usability Scale (SUS) at week 52 (year 1) and week 104 (follow-up). Range 0-100. Higher score indicate better usability.
Measured: week 104 (follow-up)
Barriers and motivators to engage in physical activity
Barriers and motivators to engage in physical activity reported on a self-developed questionnaire
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in phenoconversion neurodegenerative disease
Change from baseline (week 0) on phenoconversion in Parkinson's Disease (PD), Lewy body dementia (LBD) and multiple system atrophy (MSA). Higher scores indicate more phenoconversion.
Measured: Week 0 (baseline) and week 104 (follow-up)
Change in step count on a group level (compliance)
Change from week -4 until 0 (baseline period) mean step count per day compared to mean step count in 6 month periods. Mean step count per day will be calculated from 4-week periods. Scored as number of participants able to increase step count per day 0-25%, 26-50%, 51-75%, 76-100% relative to their own baseline measure
Measured: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
Change in moderate to vigorous physical activity per day on a group level (compliance)
Change from week -4 until 0 (baseline period) number of minutes exerting (minimally) ≥ 64% of maximum heart rate in 6 month periods. Mean minutes per day will be calculated from 4-week periods. Scored as number of participants to increase 0-25%, 26-50%, 51-75%, 76-100% relative to their own baseline measure
Measured: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
Number of completed step week goals on a group level (compliance)
Total number of completed step count week goals
Measured: Week 0 (baseline) and week 104 (follow-up)
Number of completed aerobic activity (MVPA intensity) week goals on a group level (compliance)
Total number of completed aerobic activity (MVPA intensity) week goals
Measured: Week 0 (baseline) and week 104 (follow-up)
Number of drop-outs on a group level (retention rate)
Number of drop-outs throughout the study
Measured: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Number of interactions with Slow-SPEED app on a group level
Total times opening the app
Measured: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Number of completed questionnaires on group level (completeness of digital assessments)
Number of completed questionnaires
Measured: Week 0 (baseline), week 52, week 104 (follow-up)
Number of smartwatch data points on group level (completeness of digital assessments)
Number of data points received for each selected smartwatch parameter
Measured: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Total smartwatch wear time on group level (completeness of digital assessments)
Total smartwatch wear time
Measured: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Number of Roche PD Research mobile application data points on group level (completeness of digital assessments)
Number of data points received
Measured: Week 0 (baseline), week 6, week 12, week 18, week 24, week 30, week 36, week 42, week 48, week 54, week 60, week 66, week 72, week 78, week 84, week 90, week 96, week 102
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start15 Jan 2024
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind randomized controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Stichting ParkinsonNL, ZonMw: The Netherlands Organisation for Health Research and Development, Michael J. Fox Foundation for Parkinson's Research, Parkinson's UK, Cure Parkinson's, Edmond J. Safra Foundation, Davis Phinney Foundation, Donders Centre for Cognitive Neuroimaging, Anne Wojcicki Foundation, Sleep Medicine Centre Kempenhaeghe, Sleep Medicine Centre SEIN, Queen Mary University of London, 23andMe, Inc., Parkinsons Progression Markers Initiative (PPMI), Massachusetts General Hospital, Harvard School of Public Health (HSPH), IJsfontein B.V., Netherlands, Hoffmann-La Roche, Erasmus Medical Center, University of Illinois at Chicago, University of Rochester, University of Bristol, University of Plymouth, University of Luebeck, McGill University, University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Sirwan KL Darweesh, PhD, Principal investigator, Radboudumc Department of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06193252
- Sponsor's protocol ID
- NL84072.091.23
- Acronym
- Slow-SPEED-NL
- Status last verified
- Aug 2026
- First submitted
- 21 Dec 2023
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will make relevant anonymised data available in a database.
Publications
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, Schootemeijer S, Schwarzschild MA, Simuni T, Sommerauer M, Stefani A, Steidel K, Verbeek M, van der Vliet R, de Vries NM, van de Warrenburg B, Wyse RK, Bloem BR, Schneider RB, Noyce AJ, Darweesh SKL. Slow-SPEED: protocol for three randomised trials of remotely delivered exercise to prevent Parkinson's disease. NPJ Parkinsons Dis. 2026 Jul 14. doi: 10.1038/s41531-026-01463-z. Online ahead of print.
PubMed 42448717Tolosa 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.
PubMed 41688680
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands
- ClinicalTrials.gov ID
- NCT06193252
- Acronym / sponsor ID
- Slow-SPEED-NL / NL84072.091.23
- Conditions
- Parkinson Disease, Prodromal Stage, Neurodegenerative Diseases, Parkinsonian Disorders, REM Sleep Behavior Disorder, Basal Ganglia Diseases
- Keywords
- Physical Activity, Prevention, Remote, Mobile Health (mHealth), Feasibility, Exercise, Digital biomarker, Blood
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Stichting ParkinsonNL, ZonMw: The Netherlands Organisation for Health Research and Development, Michael J. Fox Foundation for Parkinson's Research, Parkinson's UK, Cure Parkinson's, Edmond J. Safra Foundation, Davis Phinney Foundation, Donders Centre for Cognitive Neuroimaging, Anne Wojcicki Foundation, Sleep Medicine Centre Kempenhaeghe, Sleep Medicine Centre SEIN, Queen Mary University of London, 23andMe, Inc., Parkinsons Progression Markers Initiative (PPMI), Massachusetts General Hospital, Harvard School of Public Health (HSPH), IJsfontein B.V., Netherlands, Hoffmann-La Roche, Erasmus Medical Center, University of Illinois at Chicago, University of Rochester, University of Bristol, University of Plymouth, University of Luebeck, McGill University, University of Pittsburgh
- Study start
- 15 Jan 2024 (actual)
- Primary completion
- 1 Dec 2028 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 5 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone applicationLarge proportional increase in step count and minutes exerting moderate to vigorous physical activity (MVPA) relative to baseline level. |
| Active control | Active comparator | Behavioral: Increase of physical activity volume and intensity with the use of a motivational smartphone applicationSmall proportional increase in step count and minute exerting moderate to vigorous physical activity (MVPA) relative to baseline level. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Increase of physical activity volume and intensity with the use of a motivational smartphone applicationA 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 physical activity goal (i.e. incremental relative increase of step count and minutes exerting ≥ 64% of maximum heart rate reflecting MVPA relative to baseline level.). | Behavioural | Active control, Intervention |
Primary outcome
Mean change in step count per day
Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
Mean change in step count per day as measured continuously with a smartwatch. Mean steps per day will be calculated from 4-week periods. Higher positive change in step count indicate more volume of physical activity.
44 secondary outcomes
Change in moderate to vigorous physical activity (MVPA) per day
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in VO2max (physical fitness)
Time frame: 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)
Time frame: 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)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in anxiety and depression (HADS)
Time frame: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
Change in cognition (MoCA)
Time frame: Week 0 (baseline), week 104 (follow-up)
Mean change in light sleep (sleep stage)
Time frame: 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)
Time frame: 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)
Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
Change in self-reported sleep quality (PSQI)
Time frame: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
Change in olfaction (UPSIT)
Time frame: Week 0 (baseline), week 104 (follow-up)
Change in motor symptoms (Roche PD Research mobile application)
Time frame: Week 0 (baseline), week 6, week 12, week 18, week 24, week 30, week 36, week 42, week 48, week 54, week 60, week 66, week 72, week 78, week 84, week 90, week 96, week 102
Change in metabolism (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in inflammation (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in growth factors (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in ageing mechanism (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in pathological protein (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in neurodegeneration (blood based biomarkers)
Time frame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
Change in brain volume (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in white matter hyperintensities (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in basal ganglia; cortex [1] (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in basal ganglia; cortex [2] (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [1] (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [2] (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in substantia nigra [3]; locus coeruleus (imaging biomarkers)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in instrumental activities of daily living (ADL) (functional status)
Time frame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
Change in WHOQoL-BREF (quality of life)
Time frame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
Change in Research and Development (RAND-36)/Short Form health survey (SF-36) (quality of life)
Time frame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
System Usability (SUS)
Time frame: week 104 (follow-up)
Barriers and motivators to engage in physical activity
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in phenoconversion neurodegenerative disease
Time frame: Week 0 (baseline) and week 104 (follow-up)
Change in step count on a group level (compliance)
Time frame: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
Change in moderate to vigorous physical activity per day on a group level (compliance)
Time frame: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
Number of completed step week goals on a group level (compliance)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Number of completed aerobic activity (MVPA intensity) week goals on a group level (compliance)
Time frame: Week 0 (baseline) and week 104 (follow-up)
Number of drop-outs on a group level (retention rate)
Time frame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Number of interactions with Slow-SPEED app on a group level
Time frame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Derived from this study: PubMed 42448717Oosterhof 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, Schootemeijer S, Schwarzschild MA, Simuni T, Sommerauer M, Stefani A, Steidel K, Verbeek M, van der Vliet R, de Vries NM, van de Warrenburg B, Wyse RK, Bloem BR, Schneider RB, Noyce AJ, Darweesh SKL. Slow-SPEED: protocol for three randomised trials of remotely delivered exercise to prevent Parkinson's disease. NPJ Parkinsons Dis. 2026 Jul 14. doi: 10.1038/s41531-026-01463-z. Online ahead of print.
- Derived from this study: PubMed 41688680Tolosa 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.
- Individual participant dataSharing planned: Yes. We will make relevant anonymised data available in a database.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sirwan KL Darweesh, PhD principal investigator
Radboudumc Department of Neurology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Increase of physical activity volume and intensity with the use of a motivational smartphone application in people with Parkinson Disease and Prodromal Stage, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thomas Oosterhof, MSc (0031631647857, thomas.oosterhof@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change in step count per day (time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06193252, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026; AzTrials last refreshed its copy on 26 Oct 2026.