Clinical trial NCT06993142: Slow-SPEED: Slowing Parkinson's Early Through Exercise Dosage
Official title: Slow-SPEED: Slowing Parkinson's Early Through Exercise Dosage
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson Disease
Prodromal Stage
Neurodegenerative Diseases
Basal Ganglia Diseases
Central Nervous System Diseases
Synucleinopathies
Nervous System Diseases
Cerebral Disorder
Brain Diseases
Parkinsonian Disorders
Genetic Predisposition
Keywords: Physical activity
Prevention
Remote
Mobile Health (mHealth)
Feasibility
Exercise
Digital biomarker
Motivational application
Walking
Parkinson Disease
Prodromal
LRRK2
GBA1
Genetic
Smartwatch
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: 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
name: Donders Centre for Cognitive Neuroimaging
name: Parkinson's Foundation
First posted: 2025-05-28
Enrollment: 600
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Double-blind randomized controlled trial
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is two-fold. First to investigate the feasibility of whether a remotely administered smartphone app can increase the volume and intensity of physical activity in daily life in individuals with a LRRK2 G2019S or GBA1 N370S genetic mutation over a long period of time (24 months). Second, to explore the preliminary efficacy of exercise on markers for prodromal Parkinson's disease progression in individuals with a LRRK2 G2019S or GBA1 N370S genetic mutation.

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. A joint primary objective consists of two components. First to determine the longitudinal effect of an exercise intervention in LRRK2 G2019S or GBA1 N370S variant carriers on a prodromal load score, comprised of digital biomarkers of prodromal symptoms. The secondary component of the primary outcome is to determine the feasibility of a remote intervention study. The secondary objective is the effect of a physical activity intervention on digital markers of physical fitness. Exploratory outcomes entail retention rate, completeness of remote digital biomarker assessments, digital prodromal motor and non-motor features of PD. Using these biomarkers, the investigators 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 Kingdom are currently in preparation (Slow-SPEED-UK) and active in the Netherlands (Slow-SPEED-NL). 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 a LRRK2 G2019S or GBA1 N370S genetic mutation have an increased risk to develop clinically manifest PD. Therefore, this group is likely to develop 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 prodromal PD using a newly developed, fully remote smartphone-based app. The app is inspired by the app used in the STEPWISE trial (NCT04848077) and currently used in Slow-SPEED-NL (NCT06193252).

Objective: The joint primary objective has two components. First, to evaluate the long-term (36-month) impact of an exercise intervention on a prodromal load score in individuals carrying the LRRK2 G2019S or GBA1 N370S variants. This score will be derived from digital biomarkers capturing both motor and non-motor prodromal symptoms. Using these biomarkers, the investigators aim to develop a composite prodromal load score to estimate the overall burden of prodromal features.

The secondary component of the primary outcome is to determine the feasibility of a long-term (36 months) remote intervention study expressed as longitudinal change in digital measures of physical activity (step count) measured using a Fitbit smartwatch.

Our secondary objective is the potential group effect on physical fitness. Thirdly, the investigators investigate whether the intervention, prodromal motor- and non-motor symptoms can be assessed remotely in a digital, decentralized fashion.

Currently blood- and imaging biomarkers are not incorporated as outcome measures. The investigators intend to add these biomarkers pending appropriate funding.

Study design: Double-blind randomized controlled trial

Study population: A total of 600 English speaking individuals living in the United States of America with a LRRK2 G2019S or GBA1 N370S genetic mutation 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. Participant recruitment will primarily target individuals from the 23andMe customer base. Enrollment and onboarding of study participants will be supported by research staff at the University of Rochester.

Intervention: Participants will be randomized to a group (1:1 ratio) and will be motivated to increase the volume and intensity of physical activity based on their own baseline level. Baseline physical activity levels will be determined during a 4-week period. The two groups differ in the amount of physical activity that they are tasked to achieve.

Eligibility criteria: Inclusion criteria

1. previously identified LRRK2 G2019S or GBA N370S variant based on genotyping
2. aged 50 years or older
3. able to understand the English language
4. being able to walk independently inside the home without the use of a walking aid
5. in possession of a suitable smartphone (screen size minimum 4.6 inch), (Android version 9 or iOS version 15 or newer)
6. Not in a high physical activity range during the 4-week eligibility and baseline period

Exclusion criteria

1. clinically diagnosed or self-reported diagnosis neurodegenerative disease
2. self-reported falls of three or more per year
3. dexterity problems or cognitive impairments hampering smartphone use
4. if they are not aware of and do not wish to be informed about an increased risk of developing diseases associated with the LRRK2 or GBA1 risk variant
5. if individual is not community-dwelling
6. in possession of one of the following devices: Huawei P8 Lite; Huawei P9 Lite; Xiaomi Mi 6; Huawei P20 Lite (Fitbit is incompatible)

Primary outcomes:
measure: Change in composite prodromal load score
timeFrame: From inclusion (week 0) to the end of treatment (week 156)
measure: Mean change in step count per day
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
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 152 until 156 (end of treatment)
measure: Change in resting heart rate (physical fitness)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Change in heart rate variability (physical fitness & autonomic function)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Change in VO2max (physical fitness)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Change in anxiety and depression (HADS)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Change in cognition (CANTAB web-version)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Mean change in light sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Mean change in deep sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Mean change in REM sleep (sleep stage)
timeFrame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)
measure: Change in self-reported sleep quality (PSQI)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Change in REM-sleep behavior disorder (RBDSQ)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Change in olfaction (UPSIT)
timeFrame: Week 0 (baseline), week 156 (end of treatment)
measure: Change in motor symptoms (Roche PD Research mobile application)
timeFrame: Week 0, 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, Week 108, Week 114, Week 120, Week 126, Week 132, Week 138, Week 144, Week 150, Week 156
measure: Change in instrumental activities of daily living (ADL) (functional status)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Change in WHOQoL-BREF (quality of life)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
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), week 104 (2 years), week 156 (end of treatment)
measure: Change in MDS-UPDRS part 1b (Non-Motor Experiences of Daily Living)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Change in MDS-UPDRS part 2 (Motor Experiences of Daily Living)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: System Usability (SUS)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
measure: Barriers and motivators to engage in physical activity
timeFrame: Week 0 (baseline) and week 156 (end of treatment)
measure: Change in phenoconversion neurodegenerative disease (0-100%)
timeFrame: Week 0 (baseline) and week 156 (end of treatment)
measure: Change in REM-sleep behavior disorder diagnosis
timeFrame: Week 0 (baseline) and week 156 (end of treatment)
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, Week 104-130, Week 130-156
measure: Change in moderate to vigorous physical activity per day on a group level (compliance)
timeFrame: Week 0-26, Week 26-52, Week 52-78, Week 78-104, Week 104-130, Week 130-156
measure: Number of completed step week goals on a group level (compliance)
timeFrame: Week 0 (baseline) and week 156 (end of treatment)
measure: Number of completed aerobic activity (MVPA intensity) week goals on a group level (compliance)
timeFrame: Week 0 (baseline) and week 156 (end of treatment)
measure: Number of drop-outs on a group level (retention rate)
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104, week 130, week 156 (end of treatment)
measure: Number of interactions with Slow-SPEED app on a group level
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104, week 130, week 156 (end of treatment)
measure: Number of completed questionnaires on group level (completeness of digital assessments)
timeFrame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)
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, week 130, week 156 (end of treatment)
measure: Total smartwatch wear time on group level (completeness of digital assessments)
timeFrame: Week 0 (baseline), week 26, week 52, week 78, week 104, week 130, week 156 (end of treatment)
measure: Number of Roche PD Research mobile application data points on group level (completeness of digital assessments)
timeFrame: Week 0, 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, Week 108, Week 114, Week 120, Week 126, Week 132, Week 138, Week 144, Week 150, Week 156
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester Center for Health and Technology (CHeT)
state: New York
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: