Blood Lactate Concentrations With and Without Exercise in Parkinson's Disease and Multiple Sclerosis Patients
| Status: | Completed |
|---|---|
| Conditions: | Parkinsons Disease, Neurology, Neurology, Multiple Sclerosis |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 45 - 90 |
| Updated: | 4/21/2016 |
| Start Date: | August 2014 |
| End Date: | December 2014 |
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
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.
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.
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.
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.
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
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