Slow-SPEED: Slowing Parkinson's Early Through Exercise Dosage
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Increase of physical activity volume and intensity with the use of a motivational smartphone application.
- Who it may be relevant to
- Registry conditions: Parkinson Disease, Prodromal Stage, Neurodegenerative Diseases, Basal Ganglia Diseases. Basic parameters: from 50 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Netherlands
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Behavioral 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 phys
Primary outcome measures
- Change in composite prodromal load score [Time frame: From inclusion (week 0) to the end of treatment (week 156)]
- Mean change in step count per day [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
Secondary outcome measures (12)
- 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 152 until 156 (end of treatment)]
- Change in resting heart rate (physical fitness) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Change in heart rate variability (physical fitness & autonomic function) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Change in VO2max (physical fitness) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Change in anxiety and depression (HADS) [Time frame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
- Change in cognition (CANTAB web-version) [Time frame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
- Mean change in light sleep (sleep stage) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Mean change in deep sleep (sleep stage) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Mean change in REM sleep (sleep stage) [Time frame: All 4 week periods between and including week -4 until 0 (baseline period) and week 152 until 156 (end of treatment)]
- Change in self-reported sleep quality (PSQI) [Time frame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
- Change in REM-sleep behavior disorder (RBDSQ) [Time frame: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
- Change in olfaction (UPSIT) [Time frame: Week 0 (baseline), week 156 (end of treatment)]
Eligibility 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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Double blind
- Primary purpose
- Prevention
Study locations
United States · 1 center
- University of Rochester Center for Health and Technology (CHeT) — Rochester
Netherlands · 1 center
- Radboud University Medical Center — Nijmegen
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, S PMID 42448717
Identifiers
NCT: NCT06993142 · IRB ID: 13495 · PF-Trail-1421986