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

NCT ID: NCT06993142

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 600 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2029-06-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Large increase in step count and moderate to vigorous physical activity relative to baseline level.

Group Type: EXPERIMENTAL

Increase of physical activity volume and intensity with the use of a motivational smartphone application

Intervention Type: BEHAVIORAL

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 moderate-to-vigorous physical activity (MVPA) relative to baseline level).

Small increase in step count and moderate to vigorous physical activity relative to baseline level.

Group Type: ACTIVE_COMPARATOR

Increase of physical activity volume and intensity with the use of a motivational smartphone application

Intervention Type: BEHAVIORAL

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 moderate-to-vigorous physical activity (MVPA) relative to baseline level).

Interventions

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 physical activity goal (i.e. incremental relative increase of step count and minutes exerting ≥ 64% of maximum heart rate reflecting moderate-to-vigorous physical activity (MVPA) relative to baseline level).

Intervention Type: BEHAVIORAL

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)

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting ParkinsonNL

UNKNOWN

Sponsor Role: collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

Parkinson's UK

OTHER

Sponsor Role: collaborator

Cure Parkinson's

OTHER

Sponsor Role: collaborator

Edmond J. Safra Foundation

UNKNOWN

Sponsor Role: collaborator

Davis Phinney Foundation

OTHER

Sponsor Role: collaborator

Sleep Medicine Centre Kempenhaeghe

OTHER

Sponsor Role: collaborator

Sleep Medicine Centre SEIN

UNKNOWN

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: collaborator

23andMe, Inc.

INDUSTRY

Sponsor Role: collaborator

Parkinsons Progression Markers Initiative (PPMI)

UNKNOWN

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

IJsfontein B.V., Netherlands

UNKNOWN

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: collaborator

University of Bristol

OTHER

Sponsor Role: collaborator

University of Plymouth

OTHER

Sponsor Role: collaborator

University of Luebeck

OTHER

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Donders Centre for Cognitive Neuroimaging

OTHER

Sponsor Role: collaborator

Parkinson's Foundation

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sirwan KL Darweesh, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboudumc Department of Neurology

Locations

University of Rochester Center for Health and Technology (CHeT)

Rochester, New York, United States

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Countries

United States; Netherlands

Central Contacts

Thomas Oosterhof, MSc

Role: CONTACT

thomas.oosterhof@radboudumc.nl

0031631647857

Facility Contacts

Karen Clark

Role: primary

karen.clark@chet.rochester.edu

585-275-7311

Thomas H Oosterhof, MSc

Role: primary

info@onderzoek-bws.nl

+31631647857

Other Identifiers

PF-Trail-1421986

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB ID: 13495

Identifier Type: -

Identifier Source: org_study_id