Clinical trial NCT06193252: Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands
Official title: Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Prodromal Stage
Neurodegenerative Diseases
Parkinsonian Disorders
REM Sleep Behavior Disorder
Basal Ganglia Diseases
Central Nervous System Diseases
Synucleinopathies
Nervous System Diseases
Cerebral Disorder
Brain Diseases
Keywords: Physical Activity
Prevention
Remote
Mobile Health (mHealth)
Feasibility
Exercise
Digital biomarker
Blood
Imaging
MRI
Motivational application
Walking
Parkinson Disease
Prodromal
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Stichting ParkinsonNL
name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Michael J. Fox Foundation for Parkinson's Research
name: Parkinson's UK
name: Cure Parkinson's
name: Edmond J. Safra Foundation
name: Davis Phinney Foundation
name: Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen
name: Anne Wojcicki Foundation
name: Sleep Medicine Centre Kempenhaeghe
name: Sleep Medicine Centre SEIN
name: Queen Mary University of London
name: 23andMe, Inc.
name: Parkinsons Progression Markers Initiative (PPMI)
name: Massachusetts General Hospital
name: Harvard School of Public Health (HSPH)
name: IJsfontein B.V., Netherlands
name: Hoffmann-La Roche
name: Erasmus Medical Center
name: University of Illinois at Chicago
name: University of Rochester
name: University of Bristol
name: University of Plymouth
name: University of Luebeck
name: McGill University
name: University of Pittsburgh
First posted: 2024-01-05
Enrollment: 110
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind randomized controlled trial
Primary purpose: PREVENTION

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Mean change in step count per day
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
Secondary outcomes:
measure: Change in moderate to vigorous physical activity (MVPA) per day
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in resting heart rate (physical fitness)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in heart rate variability (physical fitness)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in blood pressure (physical fitness)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in VO2max (physical fitness)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in heart rate variability (autonomic function)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in orthostatic blood pressure (autonomic function)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in anxiety and depression (HADS)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
measure: Change in cognition (MoCA)
timeFrame: Week 0 (baseline), week 104 (follow-up)
measure: Mean change in light sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Mean change in deep sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Mean change in REM sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 100 until 104 (follow-up period)
measure: Change in self-reported sleep quality (PSQI)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (follow-up)
measure: Change in olfaction (UPSIT)
timeFrame: Week 0 (baseline), week 104 (follow-up)
measure: Change in motor symptoms (Roche PD Research mobile application)
timeFrame: 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
measure: Change in metabolism (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in inflammation (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in growth factors (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in ageing mechanism (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in pathological protein (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in neurodegeneration (blood based biomarkers)
timeFrame: Week 0 (baseline), week 26 (optional), week 52 (optional), week 78 (optional) and week 104 (follow-up)
measure: Change in brain volume (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in white matter hyperintensities (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in basal ganglia; cortex [1] (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in basal ganglia; cortex [2] (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in substantia nigra [1] (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in substantia nigra [2] (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in substantia nigra [3]; locus coeruleus (imaging biomarkers)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in instrumental activities of daily living (ADL) (functional status)
timeFrame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
measure: Change in WHOQoL-BREF (quality of life)
timeFrame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
measure: Change in Research and Development (RAND-36)/Short Form health survey (SF-36) (quality of life)
timeFrame: Week 0 (baseline), week 52 (1 year) and week 104 (follow-up)
measure: System Usability (SUS)
timeFrame: week 104 (follow-up)
measure: Barriers and motivators to engage in physical activity
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in phenoconversion neurodegenerative disease
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Change in step count on a group level (compliance)
timeFrame: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
measure: Change in moderate to vigorous physical activity per day on a group level (compliance)
timeFrame: Week -4 until 0 (baseline) compared to week 0-26, week 26-52, week 52-78, week 78-104
measure: Number of completed step week goals on a group level (compliance)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Number of completed aerobic activity (MVPA intensity) week goals on a group level (compliance)
timeFrame: Week 0 (baseline) and week 104 (follow-up)
measure: Number of drop-outs on a group level (retention rate)
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
measure: Number of interactions with Slow-SPEED app on a group level
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
measure: Number of completed questionnaires on group level (completeness of digital assessments)
timeFrame: Week 0 (baseline), week 52, week 104 (follow-up)
measure: Number of smartwatch data points on group level (completeness of digital assessments)
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
measure: Total smartwatch wear time on group level (completeness of digital assessments)
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104 (follow-up)
measure: Number of Roche PD Research mobile application data points on group level (completeness of digital assessments)
timeFrame: 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
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
Study officials:
affiliation: Radboudumc Department of Neurology
name: Sirwan KL Darweesh, PhD
role: PRINCIPAL_INVESTIGATOR
References: