The ParkCycle Study: Aerobic Exercise in PD

Study Overview
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Brief Summary
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The primary goal of this study is to determine the neuroprotective qualities of long-term, in home, exercise therapy program in human PD patients. It is hypothesized that an exercise intervention might delay the onset of levo-dopa therapy (i.e. evidence for neuroprotection). The first part involves a pilot-study in which the feasibility of the intervention and outcome measures will be tested.

Detailed Description
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Neuroprotective therapy (i.e. therapy that slows the disease process) is an unmet medical need in Parkinson's disease (PD). Animal studies have shown that 'intensive' exercise improves motor function and may have neuroprotective properties. The promising animal results have not been translated to patients with PD so far. This is a two-cluster randomised control trial in which twenty patients (10 at each site) will undergo a 6-month exercise intervention on a stationary virtual reality bike and twenty patients (10 at each site)will serve as controls.

Official Title
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The ParkCycle Study: Effects of Aerobic Exercise on Cognitive and Adaptive Plasticity in Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Behavioral: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic Parkinson's disease according to the UK Queen Square Brain Bank Criteria Hoehn & Yahr disease stages I-II Age between 30 and 75 years Having insufficient physical activity according to the ACSM guideline for adults, 50-64 years old with a chronic condition Untreated with anti-parkinsonian medication or receiving medication, for less than two years, medication-responsive without fluctuations. Exclusion Criteria: Unclear diagnosis with Red Flags Advanced problems in cognitive functioning: Mini Mental State Examination (MMSE)19 score < 24 Serious co-morbidity: neurological or orthopedic disorder that severely affects movement; known by specialist or medical practitioner Pulmonary diseases; known by specialist or medical practitioner Stroke High risk of cardiovascular complications: Hypertension (systole >150 and diastole > 100) Diabetes Mellitus; known by specialist or medical practitioner Cardiac valve defect (especially aortic valve stenosis); known by specialist or medical practitioner Cardiac rhythm disorder; known by specialist or medical practitioner Heart failure; known by specialist or medical practitioner Use of ß-blockers Not able to complete American (for Cleveland site) or Dutch questionnaires (for the Nijmegen site) Daily institutionalized care Contra-indications for fMRI: Pregnancy Metallic implants or electronic devices Previous seizure Claustrophobia Not able to keep the head still for longer period, i.e. due to severe head tremor

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise<br>Twente patients will perform Aerobic exercise 3 times a week for at least 30 min | Behavioral: Exercise<br>* six-months long exercise intervention on a stationary virtual reality bike, 3-5 times a week, each session lasting 30-45 minutes at a target heart rate (60-85% heart rate reserve).<br>|
| No Intervention: Control<br>Fifteen patients will be listed as a control group and will be instructed to continue their previous level of activity throughout the study | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trails A and B task | this test requires subjects to connect numbers on a screen from 1 to 25 (part A) and to connect numbers to letters. This neuropsychological test has already been proven to be sensitive to frontal lobe damage (e.g. Boll 1981) and has been recognised as an outcome for executive function in PD21. This test is performed using an online system called i-COMET that allows subject to complete the task weekly at home. Subjects have to login at the i-COMET website (https://i-comet.com) with a username and password that is provided to them by the research team. | every month for 6-7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS |  | baseline and after 6 months follow-up (FU) | 
| Cognitive tests | MMSE and SCOPA-org | baseline and after 6 months FU | 
| Kinetics tests | Timed Up and Go Test (iTUG) and a postural sway test, , as an objective measure for balance and mobility Finger tap test as a measure for bradykinesia and a pegboard test as a measure for complex motor function | baseline and after 6 months FU | 
| questionaires | The PDQ-39 is a PD specific questionnaire including 39 items concerning quality of life. Other non-motor features such as mood and sleep are respectively measured using the HADS and SCOPA-Sleep. | baseline and after 6 months FU | 
| maximal exercise test | to determine training load and subject fitness | baseline and after 6 months FU | 
| feasibility parameters | Compliance based on the number of completed exercise sessions and the amount of time that patients exercised at their target heart rate. | after 6 months (termination of intervention) | 
| neuroplasticity | Volumetric brain changes: cerebral grey and white matter will be analyzed using Vox-Based Morphometry, a validated and fully automated technique for computational analysis of differences in global and local grey and/or white matter volume. Resting state brain perfusion: functional coupling between strial subregions and the cerebral cortex will be analyzed using multiple regression analyses on resting state functional MRI data. | baseline and after 6 months FU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Neuroprotective, Intensive exercise