Blood Lactate Concentrations With and Without Exercise in Parkinson's Disease and Multiple Sclerosis Patients

Study Overview
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Brief Summary
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Fatigue is one of the most common and debilitating symptoms experienced in Parkinson's Disease (PD) and Multiple Sclerosis (MS). There are multiple proposed mechanisms of disorder-related fatigue, however, it is unknown whether PD or MS patients experience compromised blood lactate responses to an acute bout of exercise, subjecting them to exercise-related fatigue. These populations may experience higher energy expenditure at rest due to increased rigidity, however, limited data exists investigating resting energy expenditure in these populations. Researchers hypothesize that PD and MS patients will display higher resting energy expenditure than healthy age-matched controls, and that level of energy expenditure will correlate with amount of rigidity or spasticity. Also, we hypothesize that baseline levels of lactate will not be different between PD/MS and control groups, but post-exercise blood lactate levels will be significantly higher in the PD/MS groups.

Detailed Description
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Patients diagnosed with Parkinson's Disease (PD) and Multiple Sclerosis (MS) frequently experience increased levels of muscle weakness and fatigue; This impairment is exacerbated with onset of exercise and alleviated with rest or sleep . Importantly, in about 1/3 of PD patients, fatigue is considered debilitating , and even further, there is inconclusive evidence suggesting that anti-PD and anti-MS drugs improve fatigue. The precise mechanisms and pathogenesis of the disorder-specific fatigue in PD and MS remain elusive. Both peripheral and central cholinergic systems are affected in PD , however, it has been shown that peripheral cholinergic neurons at the neuromuscular junction are normal functioning . Even so, recruitment of necessary motor units may be greatly affected due to peripheral neuropathy common in both PD and MS . Following repetitive nerve stimulation in PD and MS, there is consistent evidence of a decrease in the number of functioning motor units and decrements in muscle responses. This promotes progressive fatigue with decrements in the amplitude of movement. Therefore, recruitment of motor units may be a major cause of rapid fatigue in repetitive movement with PD and MS patients, even though peripheral neuromuscular junctions do not seem to be affected. In addition to skeletal muscle inefficiency, work rate and efficiency of breathing using respiratory muscles is significantly lower in a PD population during repetitive stimulation, used to simulate exercise-induced repetitive contractions. Respiratory inefficiencies in MS include, but are not limited to reduced forced vital capacity, hypoxemia, and respiratory muscle weakness. In addition to possible neurological mechanisms of PD- and MS-related fatigue, rigidity, defined as involuntary state of continuous muscle tension in PD, and spasticity and rigidity in MS may also have a profound effect on fatigue outcomes . Adequate muscle length is required for effective muscle contraction. Rigidity likely changes the length of the muscle at rest, and therefore contributes to ineffective muscle contraction when active. In addition to inefficient muscle contraction, the increased continuous active contraction, or tone, of the muscle results in an increase in resting energy expenditure compared to healthy individuals, even in pharmacologically treated PD patients. Interestingly, resting energy expenditure in MS patients was shown to be comparable to age-matched healthy controls; however, it is important to note that these MS patients remained medicated during the study. In addition, rigidity and spasticity, common in PD and MS, respectively may provide varying levels of resting energy expenditure; however, no research to date has examined these differences. In total, if more energy is being expended at rest, hypothetically, PD and MS patients will have inadequate energy stores to exercise to their respective full capacity. This could potentiate early onset of lactic acid and hydrogen accumulation in active muscle, decrease the pH of the active muscle, and contribute to early fatigue in repetitive tasks. Purportedly, the combination of early onset of skeletal and respiratory muscle fatigue, in addition to muscle rigidity would create an environment similar to that of high intensity exercise, even at low intensities or rest. The ensuing result may likely be an accumulation of lactic acid and hydrogen ions, making the muscle environment very acidic. However, changes in the levels of resting and post-exercise blood lactate levels have not been elucidated. Therefore, we are planning to measure resting energy expenditure using a ventilation face mask and a noseclip. Blood lactate will be sampled at rest, after simulated high-intensity exercise, and ten minutes after rest (when lactate significantly increases). The exercise will consist of performing 5 sets of static, shallow 120 degree squats for 1 minute, with 1 minute of seated rest between each squat. Sustained isometric contraction at 2/3 of the maximal voluntary contractile force for 2 to 3 minutes was found to occlude local blood flow enough that local oxygen stores were depleted . Muscle lactate is also increased 12-fold upon fatigue of isometric holds such as squats. This same environment of lactic acid buildup can be simulated by circulatory occlusion as well as 60-second isometric quadricep contractions . Isometric squats will be employed to observe differences in blood response in PD compared to healthy individuals. Therefore, the purpose of this study is to analyze the differences in resting energy expenditure and exercise-induced lactate production in PD and MS compared to healthy, age-matched controls.

Official Title
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Phase 1 Study of A Double-Blind Placebo-Controlled Study of the Effect of Beta-Alanine and Whole Body Vibration on Neurologic Motoric Function, Vascular Function, and Quality of Life in Parkinson's Disease

Conditions
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Parkinson's Disease, Multiple Sclerosis

Intervention / Treatment
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* Device: pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's Disease Stage I-IV (be standard criteria H&Y scale) Multiple Sclerosis Healthy, age-matched controls 45 to 90 years old Exclusion Criteria: Dementia Co-morbid neurologic factors Individuals without independent ambulation Significant heart and respiratory disease Debilitating arthritis

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood Lactate Response in PD<br>This arm involves performing 5 sets of 1-minute squats with 1 minute of rest between each, and a finger prick before, after, and 10 minutes after the exercise in a PD population. One set of the squats will be performed on a whole body vibration plate (pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)), and one on the ground. | Device: pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)<br>* Subjects will be exposed to vertical vibration with a frequency and peak-to-peak displacement of 30 Hz and 1 mm, respectively, which provides a peak-to-peak acceleration of about 4.16 G. Whole Body Vibration<br>|
| Experimental: Blood Lactate Response in MS<br>This arm involves performing 5 sets of 1-minute squats with 1 minute of rest between each, and a finger prick before, after, and 10 minutes after the exercise in an MS population. One set of the squats will be performed on a whole body vibration plate (pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)), and one on the ground. | Device: pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)<br>* Subjects will be exposed to vertical vibration with a frequency and peak-to-peak displacement of 30 Hz and 1 mm, respectively, which provides a peak-to-peak acceleration of about 4.16 G. Whole Body Vibration<br>|
| Experimental: Blood Lactate Responses in Controls<br>This arm involves performing 5 sets of 1-minute squats with 1 minute of rest between each, and a finger prick before, after, and 10 minutes after the exercise in healthy, older adults. One set of the squats will be performed on a whole body vibration plate (pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)), and one on the ground. | Device: pro5 AIRdaptive Power Plate (Badhoevedorp, The Netherlands)<br>* Subjects will be exposed to vertical vibration with a frequency and peak-to-peak displacement of 30 Hz and 1 mm, respectively, which provides a peak-to-peak acceleration of about 4.16 G. Whole Body Vibration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Lactate Response | Measured using a blood lactate analyzer, a finger prick test measured before, after, and 10 minutes after exercise | Before, immediately after, and 10 minutes after the squatting exercise protocol | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting Energy Expenditure | Measured using using indirect calorimetry with a ventilated face mask and noseclip (Parvometrics, Sandy, UT). This involves laying supine for 30 to 60 minutes. | Measured immediately upon arriving to the laboratory. Lasted approximately 25 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, Multiple Sclerosis, Fatigue, Resting Energy Expenditure, Whole Body Vibration, Exercise, Blood Lactate