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

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.

• Change in moderate to vigorous physical activity (MVPA) per day [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
• Change in cognition (CANTAB web-version) [Срок оценки: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
• Mean change in light sleep (sleep stage) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
• Change in REM-sleep behavior disorder (RBDSQ) [Срок оценки: Week 0 (baseline), week 52 (1 year), week 104 (2 years), week 156 (end of treatment)]
• Change in olfaction (UPSIT) [Срок оценки: Week 0 (baseline), week 156 (end of treatment)]