Slowing Parkinson's Early Through Exercise Dosage - United Kingdom

Early Phase 1

Withdrawn

• Conditions: Parkinson Disease; REM Sleep Behavior Disorder; Hyposmia; Anosmia
• Interventions: Device: Slow-SPEED app

• Registration Number: NCT06600438
• Lead Sponsor: Queen Mary University of London

Brief Summary

Parkinson\'s disease (PD) is a condition in which parts of the brain become progressively damaged over many years. The main symptoms of PD disease are involuntary shaking of parts of the body (tremor), stiffness and slow movement. However, research shows that people can also experience a range of other symptoms, such as smell loss (hyposmia), sleep problems, constipation, depression and anxiety. These features can be mild and generally occur many years before a person notices a change to their movement.

Currently, there is no proven way of preventing PD. However, it is possible that regular exercise might keep the symptoms at bay for a number of years. This is because exercise can help protect brain cells from damage. Regular movement also helps our brains adapt (or 'rewire) if one part becomes affected by disease. This could mean living symptom-free for longer.

Researchers in The Netherlands have developed a smartphone app, known as the 'Slow-SPEED' app. It works by encouraging people to gradually increase their exercise level over a number of years. Hopefully, this will promote long-term changes to a person's lifestyle. However, the app has not yet been tested in a large enough group of people to say for certain whether it works.

Queen Mary University of London is testing the Slow-SPEED app in a group of participants that have been recently diagnosed with PD. The app is also being tested in people who do not have PD, but may be at an increased risk of developing it in the future.

Three groups of people are being recruited:

1. Diagnosed with PD within the last three years

2. A reduced sense of smell (known as 'hyposmia' or 'anosmia'), diagnosed by a smell test

3. A condition called REM-sleep behavioural disorder, diagnosed at a sleep clinic

Study participants will be asked to use the Slow-SPEED app for 3 years. During this time, information about their movement will be collected by a smartwatch ('Fitbit'), which is linked to the app in their smartphone. Periodically, health information will be collected through questionnaires, movement tests (e.g. tapping tests on a smartphone) and smell tests. Some participants will be invited to have blood tests, but this is not necessary for everyone. Most of these tests can be performed at home. In addition, there is an in-person visit at the beginning and end of study. Combined, these tests should give a comprehensive picture of how exercise might impact the early features of PD.

Aims of the study:

* To test whether the Slow-SPEED app can successfully motivate people to increase their exercise level over several years.

* To determine whether exercise can prevent (or reduce) the early, subtle changes associated with PD.

Detailed Description

Slow-SPEED-UK is a randomised controlled trial investigating the effects of an app-based exercise programme in early/prodromal Parkinson's Disease (PD). The trial aims to recruit a total of 300 participants from the following cohorts: i) PD (diagnosed in previous 3 years), ii) smell loss or iii) REM-sleep behaviour disorder. Participants will be identified and recruited from a large, online, observational trial known as PREDICT-PD.

PREDICT-PD members meeting the inclusion/exclusion criteria will be contacted via email or telephone. The trial will be explained in detail, and written information provided. Interested participants will be sent an electronic consent form. This only covers the first 4 weeks of the trial, known as the 'baseline period'. Once consented, a Welcome Pack is sent to the participant's home address. This contains instructions on installation of the Slow-SPEED app to their personal smartphone. A Fitbit smartwatch is also provided.

Participants are then asked to wear the Fitbit smartwatch for 4 weeks, during which the step count is measured as they go about their normal activities. Once completed, those taking an average of more than 10,000 steps/day will be excluded. This is because it might not be safe to encourage highly active people to increase their exercise level.

Eligible participants will be invited for a 3 hour, in-person 'baseline visit', where a second consent form covering the main study period will be issued. A trained investigator will then review the medical history, measure blood pressure and administer questionnaires covering a variety of early PD features. Cognitive testing and smell testing are performed. A subgroup of participants will also undergo blood draws. For participants who are co-enrolled in the Parkinson\'s Progression Markers Initiative (PPMI), annual MRI data collected as part of this observational study will be reviewed.

Participants can then begin using the app in their daily life. Depending on their allocation to the treatment or active control arm, they will be motivated to increase their exercise level by 100% or 10%, respectively. The encourages a gradual, stepwise increase in physical activity. Participants are welcome to partake in their preferred form of exercise. Over the 3-year study period researchers will have access to continuous data recorded through their Fitbit, including app usage, heart rate, step count and sleep quality. A number of other assessments will be administered, listed below:

1. Movement tests - every 6 weeks, participants complete a series of tests on their smartphone e.g. finger tapping, shape drawing, reaction time tasks (15 minutes in total).

2. Questionnaires - participants are emailed an annual set of questionnaires regarding early/prodromal PD symptoms

3. Axivity AX 6 - a wrist-worn accelerometer will be posted out annually. Participants will wear it for 7-day 'bursts'. It records detailed information a participant's movement.

After 3 years, subjects are invited for a second in-person visit. All of the tests performed at the first visit will be repeated. Participants are asked for feedback on the Slow-SPEED app. At this point the study will be completed.

Primarily, Slow-SPEED-UK is a feasibility study, aiming to determine whether participants will regularly and sustainably engage with a remote exercise programme, irrespective of their symptom burden. For our secondary outcomes the trial will generate a wealth of data collected regarding prodromal/early PD features. These include measures of physical fitness (e.g. resting heart rate), non-motor features (e.g. blood pressure, constipation, neuropsychiatric symptoms, sleep quality, smell loss), motor deficits (bradykinesia, rigidity and tremor), quality of life, blood-based biomarkers and neuroimaging biomarkers (where applicable). The overarching hypothesis is that increasing exercise level will delay or slow the progression of these subtle, early PD features.

Study Timeline

• Study First Submitted: 2024-07-22
• Study First Submitted QC: 2024-09-13
• Study First Posted: 2024-09-19
• Study Start: 2025-01-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-20
• Primary Completion: 2029-07-01
• Study Completion: 2029-07-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

In order to be eligible to participate Slow-SPEED-UK, a subject must meet the following criteria:

1. Either:

   Previously diagnosed with iRBD, meeting all of the following criteria, as per the International Classification of Sleep Disorders (ICSD-3):

   1. Repeated episodes of sleep related vocalization and/or complex motor behaviours
   2. These behaviours are documented by polysomnography to occur during REM sleep or, based on clinical history of dream enactment, are presumed to occur during REM sleep
   3. Polysomnographic recording demonstrates REM sleep without atonia (RWA)
   4. The disturbance is not explained more clearly by another sleep disorder, mental disorder, medication, or substance use (the usage of beta-blockers or anti-depressant as possible luxating factor is not excluded)

   OR:

   Hyposmia, defined as olfaction less than or equal to the 15th percentile by age and sex, as determined by the University of Pennsylvania Smell Identification Test (UPSIT).

   OR:

   Idiopathic Parkinson's disease, diagnosed by a neurologist within the previous 3 years. Subjects must be at Hoehn and Yahr stage 1-3 at baseline.

2. Aged 50 years or older

3. Able to understand the English language

4. Able to walk independently inside the home without the use of any form of walking aid

5. Less than or equal to 120 minutes of sports/outdoor activities per day (question 1-22, 30 & 31) on LASA Physical Activity Questionnaire (LAPAQ))

6. Less than an average of 10,000 steps/day during the 4-week baseline period

7. In possession of a suitable smartphone (screen size minimum 4.6 inch), (Android version 9 or iOS version 15 or newer)

Exclusion Criteria

1. Clinically diagnosed or self-reported diagnosis of a neurodegenerative disease (other than PD).
2. Self-reported weekly falls in the previous 3 months
3. Dexterity problems or cognitive impairments hampering smartphone use
4. Subject not wishing to be informed about the association between iRBD/hyposmia and risk of future diseases
5. Care home residents or hospitalised persons.
6. Subject's personal smartphone is Fitbit-incompatible i.e. Huawei P8 Lite; Huawei P9 Lite; Xiaomi Mi 6; Huawei P20 Lite
7. Unable to give informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
100% exercise increase	Slow-SPEED app	Participants motivated towards a 100% increase in physical activity level over 3 years, using the Slow-SPEED app
10% exercise increase	Slow-SPEED app	Participants motivated towards a 10% increase in physical activity level over 3 years, using the Slow-SPEED app

Primary Outcome Measures

Name	Time	Method
Change in daily step count	3 years	Primarily, Slow-SPEED-UK is a feasibility study. We are looking to determine whether participants will regularly and sustainably engage with a remote exercise programme, irrespective of their symptom burden. Usage data collected via the Slow-SPEED app and Fitbit will provide a measure of this. As such, our primary outcome measure is the change in daily step count from baseline (weeks 0-4) to the final four weeks of the study period (weeks 153-157).

Secondary Outcome Measures

Name	Time	Method
Change in maximal oxygen consumption (VO2max)	3 years	VO2max is a common metric of cardiorespiratory fitness. Outcome measure is the difference in a participant's VO2max between the beginning and end of study period. Measured by the Fitbit smartwatch.
Change in average daily resting heart rate	3 years	Outcome is the change in average daily resting heart rate between the beginning and end of study period. Measured by the Fitbit smartwatch.
Change in exercise intensity (HRmax)	3 years	Exercise intensity is defined as the proportion of minutes in which ≥64% of a participant's maximum heart rate (HRmax) is reached. For each participant we will calculate the difference in total minutes of moderately intense physical activity between the beginning and end of the study period. Measured by the Fitbit smartwatch.
Change in resting blood pressure	3 years	Change in resting blood pressure between the beginning and end of study period. Measured in clinic using traditional sphygmomanometry.
Lying and standing blood pressure	3 years	Difference between supine and standing blood pressure will be measured at the beginning and end of study period, to provide an assessment of degree of orthostatic hypotension.
Montreal Cognitive Assessment (MoCA)	3 years	Completed at baseline and end of study provide a measure of association between exercise and cognitive function in prodromal/ early PD. Outcome is the change in scores over a 3 year period.
Electronic Symbol Digit Modalities Test (eSDMT)	3 years	Completed every 6 weeks provide a measure of association between exercise and cognitive function in prodromal/ early PD. Outcome is the change in scores over a 3 year period.
Lawton's scale for instrumental activities of daily living	3 years	Completed annually to provide a measure of association between exercise and functional status in prodromal/early PD. Outcome is the change in scores between over the 3 year study period.
WHO-QoL-BREF	3 years	Completed annually to provide a measure of association between exercise and overall quality of life in prodromal/ early PD. Outcome is the change in scores between the beginning and end of study period.
Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT)	3 years	Completed annually to provide a measure of association between exercise and autonomic dysfunction in prodromal/ early PD. Outcome is the change in scores over the 3 year study period.
Change in sleep quality	3 years	Sleep parameters (sleep time, efficiency, onset latency, time in certain sleep stage, total time awake, total time in bed) will be measured continuously by the Fitbit smartwatch. Outcome is the change in sleep parameters between the beginning and end of study period.
Short Form Health Survey (aka SF-36 or RAND-36)	3 years	Completed annually to provide a measure of association between exercise and disease-related quality of life in prodromal/ early PD. Outcome is the change in scores between the beginning and end of study period.
Change in heart rate variability	3 years	Outcome is the change in interbeat interval (measure of heart rate variability) between the beginning and end of study period. Measured by the Fitbit smartwatch.
Change in digital motor symptom scores	3 years	Battery of 6-weekly tests administered by the Roche PD mobile application (e.g. shape drawing, dexterity tasks, gait assessment) will provide motor symptoms scores for each domain tested. Outcome is the change in motor scores over the 3 year study period.
Hospital Anxiety and Depression Scale (HADS)	3 years	Completed annually to provide a measure of association between exercise and neuropsychiatric features in prodromal/ early PD. Outcome is the change in scores over study period.
University of Pennsylvania Smell Identification Test Scores	3 years	UPSIT performed at the beginning and end of study as a measure of olfactory function. Outcome measure is the change in total score.
Blood-based biomarkers	3 years	Biomarkers of ageing, genetic predisposition, metabolism, neuroinflammation, neurodegeneration, pathological protein propagation and growth factors will be analysed. Specific protocols are not yet determined; instead samples will all be analysed together at the end of the study to ensure the most up to date methods are used.
Genetic analysis	3 years	For consenting individuals, array-based genotyping will be performed on the NeuroBooster array (including variants in LRRK2 and GBA1). A subgroup analysis will be performed at the end of the study to determine the impact of genetic variants on trial outcome measures.
Neuroimaging biomarkers	3 years	We will examine the change in four markers of cerebral structure and function over the three year study period.; i. Structural changes in brain volume: Cerebral grey and white matter volume will be analysed using Voxel-Based Morphometry (VBM); ii. Resting state functional connectivity (rs-fMRI): functional coupling between striatal subregions and the cerebral cortex.; iii. Diffusion Tensor Imaging (DTI): structural integrity of the substantia nigra will be measured using free water imaging; iv. Neuromelanin-sensitive MRI: structural integrity of the locus coeruleus (LC) and the substantia nigra will be measured.
Qualitative feedback questionnaires	3 years	For app-related feedback, the System Usability Scale will be sent to participants annually. Answers will be used improve the user experience. At the end of the study a self-designed questionnaire will be used to explore motivators and barriers to engagement in physical activity. None of the above will be subject to statistical analysis.
Compliance (step count)	3 years	* Number of participants in the intervention group reaching an increase in mean step count per day of 0-25%, 26-50%, 51-75%, 76-100% relative to their baseline measurement at the end of the study period.; * Number of participants in the active-control group reaching an increase in mean step count per day of 0-25%, 26-50%, 51-75%, 76-100% relative to their baseline measurement at the end of the study period.
Compliance (exercise intensity)	3 years	* Number of participants in the intervention group reaching an increase in mean minutes with moderate to vigorous physical activity per day of 0-25%, 26-50%, 51-75%, 76-100% relative to their baseline measurement at the end of the study period.; * Number of participants in the active-control group reaching an increase in mean minutes with moderate to vigorous physical activity per day of 0-25%, 26-50%, 51-75%, 76-100% relative to their baseline measurement at the end of the study period.
Compliance (weekly step goal)	3 years	* Number of completed weekly step goals in the intervention group at the end of the study.; * Number of completed weekly step goals in the active-control group at the end of the study.
Compliance (weekly intensity goal)	3 years	* Number of completed weekly intensity goals in the intervention group at the end of the study.; * Number of completed weekly intensity goals in the active-control group at the end of the study.
Retention	3 years	* Number of participants in the intervention group who dropped out 6, 12, 18, 24, 30 and 36 months after treatment initiation; * Number of participants in the active-control group who dropped out 6, 12, 18, 24, 30 and 36 after treatment initiation
Compliance - interaction with the app	3 years	* Total times opening the Slow-SPEED app at baseline period (0-1 month; T0 - T1); * Total times opening the Slow-SPEED app in the intervention group after treatment initiation between ≥1 to ≤7 months, \>7 to ≤13 months, \>13 to ≤19 months, \>19 to ≤25 months, \>25 to ≤31 months and \>31 to ≤37 months.; * Total times of opening the Slow-SPEED app in the active-control group after treatment initiation between ≥1 to ≤7 months, \>7 to ≤13 months, \>13 to ≤19 months, \>19 to ≤25 months, \>25 to ≤31 months and \>31 to ≤37 months.
Compliance with digital assessments	3 years	* Number completed questionnaires received at treatment initiation (T1), after 1 year (T13), 2 years (T25) and at the end of study (T37).; * Number of data points received from Fitbit regarding step count and heart rate in the baseline period.; * Number of data points received from Fitbit regarding step count, heart rate, heart rate variability, VO2max, sleep parameters after treatment initiation between ≥1 to ≤7 months, \>7 to ≤13 months, \>13 to ≤19 months, \>19 to ≤25 months, \>25 to ≤31 months and \>31 to ≤37 months.; * Mean total Fitbit wear time per day derived from total of received heart rate data points (1 data point reflects 1 minute) over the whole study period.; * Number of data points received from the Roche PD Mobile app in the intervention- and active control group over the whole study period.
Phenoconversion to PD or related degenerative disease	3 years	We will determine the number of prodromal participants that have 'phenoconverted' to PD, Multiple System Atrophy and Lewy Body Dementia at the end of the study period through an in-person assessment of the clinical history and examination.
Change in MDS-UPDRS scores (Parts I, II, III)	3 years	MDS-Unified Parkinson's Disease Rating Scale will be performed at the beginning and end of study. Change in total scores will provide a measure of motor symptoms, cognition, mood, autonomic function and sleep quality.
Pittsburgh Sleep Quality Index (PSQI)	3 years	Completed annually to provide a measure of association between exercise and sleep quality in prodromal/ early PD. Outcome is the change in scores over the 3 year study period.