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

Radboud University Medical Center

Status

Not yet enrolling

Conditions

Basal Ganglia Diseases

Synucleinopathies

Genetic Predisposition

Parkinsonian Disorders

Neurodegenerative Diseases

Prodromal Stage

Central Nervous System Diseases

Parkinson Disease

Nervous System Diseases

Cerebral Disorder

Brain Diseases

Treatments

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

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06993142

IRB ID: 13495

PF-Trail-1421986 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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.

Enrollment

600 estimated patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

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

Exclusion criteria

clinically diagnosed or self-reported diagnosis neurodegenerative disease
self-reported falls of three or more per year
dexterity problems or cognitive impairments hampering smartphone use
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
if individual is not community-dwelling
in possession of one of the following devices: Huawei P8 Lite; Huawei P9 Lite; Xiaomi Mi 6; Huawei P20 Lite (Fitbit is incompatible)