Clinical trial NCT06600438: Slowing Parkinson's Early Through Exercise Dosage - United Kingdom
Official title: Slowing Parkinson's Early Through Exercise Dosage - United Kingdom
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Parkinson Disease
REM Sleep Behavior Disorder
Hyposmia
Anosmia
Keywords: Parkinson's Disease
Parkinson Disease
Anosmia
Hyposmia
Smell loss
Exercise
Prevention
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2024-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Parkinson\&amp;#39;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\&amp;#39;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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in daily step count
timeFrame: 3 years
Secondary outcomes:
measure: Change in maximal oxygen consumption (VO2max)
timeFrame: 3 years
measure: Change in average daily resting heart rate
timeFrame: 3 years
measure: Change in exercise intensity (HRmax)
timeFrame: 3 years
measure: Change in resting blood pressure
timeFrame: 3 years
measure: Lying and standing blood pressure
timeFrame: 3 years
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: 3 years
measure: Electronic Symbol Digit Modalities Test (eSDMT)
timeFrame: 3 years
measure: Lawton's scale for instrumental activities of daily living
timeFrame: 3 years
measure: WHO-QoL-BREF
timeFrame: 3 years
measure: Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT)
timeFrame: 3 years
measure: Change in sleep quality
timeFrame: 3 years
measure: Short Form Health Survey (aka SF-36 or RAND-36)
timeFrame: 3 years
measure: Change in heart rate variability
timeFrame: 3 years
measure: Change in digital motor symptom scores
timeFrame: 3 years
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3 years
measure: University of Pennsylvania Smell Identification Test Scores
timeFrame: 3 years
measure: Blood-based biomarkers
timeFrame: 3 years
measure: Genetic analysis
timeFrame: 3 years
measure: Neuroimaging biomarkers
timeFrame: 3 years
measure: Qualitative feedback questionnaires
timeFrame: 3 years
measure: Compliance (step count)
timeFrame: 3 years
measure: Compliance (exercise intensity)
timeFrame: 3 years
measure: Compliance (weekly step goal)
timeFrame: 3 years
measure: Compliance (weekly intensity goal)
timeFrame: 3 years
measure: Retention
timeFrame: 3 years
measure: Compliance - interaction with the app
timeFrame: 3 years
measure: Compliance with digital assessments
timeFrame: 3 years
measure: Phenoconversion to PD or related degenerative disease
timeFrame: 3 years
measure: Change in MDS-UPDRS scores (Parts I, II, III)
timeFrame: 3 years
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 3 years
Other outcomes:
Locations:
Study officials:
affiliation: Centre for Preventive Neurology, Queen Mary University of London
name: Alastair J Noyce, BMedSci, MBBS, MSc, MRCP, PhD
role: PRINCIPAL_INVESTIGATOR
References: