Physical Training for People With Parkinson's Disease and Multiple Sclerosis: Effect on Mind and Body

Study Overview
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Brief Summary
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People with Parkinson's disease and Multiple Sclerosis experience disabling motor and non-motor symptoms, which respond insufficiently to medication. To adequately alleviate disease burden, physical training is increasing acknowledged as an assisting therapy; however, the optimal dose of exercise in unknown.

Detailed Description
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Next to complex motor deficits, people with Parkinson's disease and Multiple Sclerosis experience highly disabling non-motor symptoms; for example, anxiety and depression, cognitive decline, fatigue, and sleep problems. Physical training is increasingly recognized as an assisting and, importantly, safe therapy for these patients to alleviate disease burden. However, the optimal dose (i.e., type, frequency, intensity, duration) of exercise has not yet been established. This study aims to investigate differences in response patterns of motor and non-motor symptoms, blood-based biomarkers of neuroplasticity and neurodegeneration, as well as functional brain connectivity to eight weeks of high intensity interval training [2x/week,  30 min/session], continuous aerobic training [2x/week,  50 min/session], or movement advice [+3000 steps/day for 5 days/week monitored with an activity tracker]. Frequently repeated assessment of outcomes measures will be conducted.

Official Title
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Physical Training for People With Parkinson's Disease and Multiple Sclerosis: Effect on Mind and Body

Conditions
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Parkinson Disease, Multiple Sclerosis

Intervention / Treatment
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* Behavioral: High Intensity Interval Training (HIIT)
* Behavioral: Continuous Aerobic Training (CAT)
* Behavioral: Movement Advice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Parkinson's Disease (PD) or Progressive Multiple Sclerosis (MS) Hoehn & Yahr stage <4 (PD), Expanded Disability Status Scale score <6 (MS) Anxiety and/or depressive symptoms; Hospital Anxiety and Depression Scale (HADS) score >=8 points on HADS-A and/or HADS-D Sufficient cognitive ability to understand training instructions; Montreal Cognitive Assessment score >21 points Able to participate in intensive physical training, no contra-indications for exercise Stable medication regime for at least 4 weeks prior to inclusion Age >=18 years Exclusion Criteria: Participation in intensive exercise program in the month prior to inclusion Relapse in the month prior to inclusion (MS) Symptoms indicating cardiovascular, pulmonary, or metabolic disease or cardiovascular, pulmonary, or metabolic disease which are not under control with medication abnormal electrocardiography in rest

Ages Eligible for Study
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Minimum Age: 18 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: Physical Training Group 1 (n=16)<br>High Intensity Interval Training | Behavioral: High Intensity Interval Training (HIIT)<br>* 8 weeks of HIIT, 2x/week for about 30 minutes/session on a cycle ergometer<br>|
| Experimental: Physical Training Group 2 (n=16)<br>Continuous Aerobic Training | Behavioral: Continuous Aerobic Training (CAT)<br>* 8 weeks of CAT, 2x/week for about 50 minutes/session on a cycle ergometer<br>|
| Experimental: Physical Training Group 3 (n=16)<br>Movement Advice | Behavioral: Movement Advice<br>* Weekly step goal, monitored using an activity tracker, +3000 steps/day for 5 days/week, step goal is based on average step count in the 4 weeks of baseline prior to the intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anxiety and depressive symptoms | The effect of physical training on anxiety and depressive symptoms, measured by the Hospital Anxiety and Depression Scale | Baseline (week 0), week 4, week 12, week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease severity | The effect of physical training on disease severity, measured by the Unified Parkinson's Disease Rating Scale (Parkinson's disease) (total score range 0-199, higher score = worse) or Expanded Disability Status Scale (Multiple Sclerosis) | Baseline (week 0), week 4, week 12, week 16 | 
| Change in cognitive function (i.e., ability to inhibit cognitive interference) | The effect of physical training on cognitive function, measured by the Stroop Color Word Test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in cognitive function (i.e., mental flexibility) | The effect of physical training on cognitive function, measured by the Trail Making Test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in cognitive function (i.e., range of cognitive operations: motor speed, attention, and visuoperceptual functions) | The effect of physical training on cognitive function, measured by the Symbol Digit Modalities Test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in fatigue | The effect of physical training on fatigue, measured by the Checklist Individual Strength fatigue sub-scale | Baseline (week 0), week 4, week 12, week 16 | 
| Change in sleep quality | The effect of physical training on sleep quality, measured by the Insomnia Severity Index | Baseline (week 0), week 4, week 12, week 16 | 
| Change in well-being | The effect of physical training on well-being, measured by the Parkinson's Disease Questionnaire (8 items) (Parkinson's disease) or Multiple Sclerosis Impact Scale (29 items) (Multiple Sclerosis) | Baseline (week 0), week 4, week 12, week 16 | 
| Change in quality of life | The effect of physical training on quality of life, measured by the Short Form health survey (36 items) | Baseline (week 0), week 4, week 12, week 16 | 
| Change in motor capacity (i.e., walking speed) | The effect of physical training on motor capacity, measured by the 10-Meter Walk Test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in motor capacity (i.e., lower extremity function, mobility, and fall risk) | The effect of physical training on motor capacity, measured by the Timed Up and Go test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in motor capacity (i.e., finger dexterity) | The effect of physical training on motor capacity, measured by the Nine Hole Peg Test | Baseline (week 0), week 4, week 12, week 16 | 
| Change in activities of daily living | The effect of physical training on activities of daily living, measured by the Nottingham Extended Activities of daily living Index | Baseline (week 0), week 4, week 12, week 16 | 
| Change in biomarkers of neuroplasticity in blood | The effect of physical training on biomarkers of neuroplasticity in blood, measured by Brain Derived Neurotrophic Factor concentration | Baseline (week 0), week 4, week 12, week 16 | 
| Change in biomarkers of neurodegeneration in blood | The effect of physical training on biomarkers of neurodegeneration in blood, measured by Neurofilament Light concentration | Baseline (week 0), week 4, week 12, week 16 | 
| Change in brain morphology | The effect of physical training on brain morphology, measured by structural magnetic resonance imaging (MRI) | Week 4, week 12 | 
| Change in structural brain connectivity | The effect of physical training on structural brain connectivity, measured by diffusion MRI + free-water content | Week 4, week 12 | 
| Change in brain connectivity | The effect of physical training on brain connectivity, measured by resting state functional MRI | Week 4, week 12 | 
| Change in brain iron concentration in the Substantia Nigra | The effect of physical training on brain iron concentration in the Substantia Nigra, measured by Quantitative Susceptibility Mapping methodology | Week 4, week 12 | 
| Change in brain neuromelanin content | The effect of physical training on brain neuromelanin content, measured by neuromelanin-sensitive MRI | Week 4, week 12 | 
| Change in daily mood | The effect of physical training on daily mood, measured by the Visual Analogue Scale (total sore range 0-10, higher score = better) | Weekly assessment from baseline to week 16 | 
| Change in daily anxiety | The effect of physical training on daily anxiety, measured by the Visual Analogue Scale (total sore range 0-10, higher score = better) | Weekly assessment from baseline to week 16 | 
| Change in daily ability to concentrate | The effect of physical training on daily ability to concentrate, measured by the Visual Analogue Scale (total sore range 0-10, higher score = better) | Weekly assessment from baseline to week 16 | 
| Change in daily fatigue | The effect of physical training on daily fatigue, measured by the Visual Analogue Scale (total sore range 0-10, higher score = better) | Weekly assessment from baseline to week 16 | 
| Change in daily sleep quality | The effect of physical training on daily sleep quality, measured by the Visual Analogue Scale (total sore range 0-10, higher score = better) | Weekly assessment from baseline to week 16 |