Glymphatic System, Parkinson's Disease and Parkinsonism
Conditions
Keywords
Exercise, Parkinson's, Glymphatic System
Brief summary
This study is designed to measure the change in patients diagnosed with Parkinson's disease (PD) before, during and after a 12 week exercise program.The focus of this study is the glymphatic system. The glymphatic system is a recentlydiscovered novel waste clearance pathway, in patients with Parkinson's Disease (PD).The glymphatic system acts as a waste-clearance system in the brain of vertebrate animals.The glymphatic system has been proposed in which new clearance pathways involving communication between paravascular spaces, interstitial fluid, and ultimately meningeal and dural lymphatic vessels exists, and we have provided evidence that this system may be dysfunctional in patients with Parkinson's disease with cognitive disorders. Early research suggest glymphatic function increases following exercise, this response is believed to clear beta-amyloid in the brain and may mediate the neurobehavioral response to exercise in PD. This study will use cognitive exams, neurological exams as well as specialized imaging to record data points and evaluate the glymphatic function after exercise.
Interventions
BEHAVIORALExercise--Rock Steady Boxing class
Rock Steady Boxing is a class designed specifically for those with Parkinsonism and movement difficulty using explosive and fine tuned movements as well as cognitive learning skills.
Sponsors
United States Department of Defense
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant has Parkinson's disease as defined by the UK Brain Bank Criteria. * Patient has demonstrated a positive levodopa or related therapy response. * Participant is willing and able to participate in a Rock Steady Boxing class. * Participation reports a typically sedentary lifestyle in the 6 months prior to enrollment, i.e., no daily-to-weekly, guided, aerobic or non-aerobic exercise routine. * Participant agreeable to an overnight dopaminergic medication washout period. * Subject has an identified, reliable method of attending study appointments and Rock Steady Boxing classes.
Exclusion criteria
* Clinical Dementia Rating scale score \<=1 * Any contraindication or inability to tolerate brain magnetic resonance imaging (MRI) or medical conditions that may interfere with their ability to enter the scanner and/or interfere with interpretation of acquired MRI scanning data (e.g., a pacemaker or any other implanted device or condition that would preclude proximity to a strong magnetic field). * Any contraindication to overnight dopaminergic medication washout period. * Any contraindication to participation in Rock Steady Boxing. * Subject resides at a skilled nursing or dementia care facility, or admission to such a facility is planned during the study period. * Signs or symptoms of untreated obstructive sleep apnea (i.e., 3+ of the 8 STOP-Bang OSA items). Treatment-compliant OSA patients will not be excluded. * Signs of MSA, probable Alzheimer disease (according to National Institute of Neurological and Communicative Disorders and Stroke, and the Alzheimer's Disease and Related Disorders), probable vascular dementia (history of cognitive decline concurrent with evidence of cerebrovascular disease progression on neuroimaging). * Evidence of any clinically significant neurological disorder including but not limited to motor neuron disease or Amyotrophic Lateral Sclerosis (ALS), normal pressure hydrocephalus, brain tumor, seizure disorder, multiple sclerosis, or known structural brain abnormalities. * History of severe or repeated head injury. * History of encephalitis. * Subject has had a significant illness or infection requiring medical intervention in the past 30 days. * History of neuroleptic use (with the exception of pimivanserin, clozapine or quetiapine) for a prolonged period of time or within the past 6 months. * Any clinically significant hematological, autoimmune, endocrine, cardiovascular, neoplastic, renal, gastrointestinal, or other disorder that, in the Investigator's opinion, could interfere with the subject's participation in the study, place the subject at increased risk, or confound interpretation of study results. * Current enrollment in another interventional clinical study involving a therapeutic agent. * Consideration by the investigator, for any reason, that the subject is an unsuitable candidate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stroop Interference Task | baseline to 12 weeks | The stroop interference task measures Measures completion time and number of errors, both corrected and not corrected, and total errors. The low and high scores are patient dependent upon performance, and the higher the scores, the more errors have been made and the worse executive functioning. The amount of time taken on the Stroop task also correlates to having worse executive functioning with a higher completion time. |
| Change in Beta-Amyloid Levels | baseline to 12 weeks | Using MRI/PET scans to measure change from baseline to followup of beta-amyloid levels |
| Change in Hopkins Verbal Learning Test (HVLT) Scores | baseline to 12 weeks | HVLT measures verbal learning skills and memory, highest score is 36 and lowest score is 0. The higher score demonstrates better recall/recognition abilities with verbal learning. |
| Change in Movement Disorder Society--Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS) | baseline to 12 weeks | UPDRS measures ease of movement. Highest Score is 108, lowest score is 0. The higher the score, the more difficult movement is for patient. |
| Mini-Balence Evaluation Systems Test (BESTest) | baseline to 12 weeks | Mini-BESTest describes movement ability and balance in different scenarios. Highest score is 28, lowest score is 0. The higher the score, the better balance/movement in different conditions. |
| Freezing of Gait Questionnaire (FOG-Q) | baseline to 12 weeks | Measures walking gait and how stable it is. Highest score is 24, lowest is 0. The higher the score, the worse walking gait is. |
| Trail Making Test A&B (TMT) | baseline to 12 weeks | TMT measures executive functioning and error detection. Measured with time to complete trails. Higher time to complete means more difficulty with executive functioning. |
| Letter Fluency (FAS) | baseline to 12 weeks | FAS measures how many words a patient can list in a minute beginning with a certain letter (F, A, or S), relating to verbal learning and executive function. The lowest score is 0 words, and the more words listed in a minute beginning with each letter, the better executive functioning. FAS is a unitary neuropsychometric test composed of sub-tasks (F, A, S). The individual scores should not be / are not interpreted. |
| Simon Task | baseline to 12 weeks | The Simon task is another well-validated measure of inhibitory action control which has also been studied extensively in PD. This is a conflict task which measures the effect of interfering impulses on the ability to select a goal response. Scores are measured in % accuracy from 0-100, and reaction times from 0 ms and upward per item. The higher the accuracy and lower the reaction time, the better the inhibitory action control and executive functioning. The outcome we used is mean and standard deviation of reaction time (seconds) for items correctly responded to. |
| Patient Recorded Outcomes Measurement Information System-Sleep Disturbance (PROMIS-Sleep) | baseline to 12 weeks | The PROMIS measures sleep disturbance and impairment. The lowest score is an 8 and the highest is a 40. The higher the score, the worse sleep impairment or disturbance is. |
| Hospital Anxiety and Depression Scale (HADS) | baseline to 12 weeks | The HADS measures anxious and depressive feelings in patients. There are 2 parts, Anxiety, where the lowest score would be a 0 and the highest is 21, and the higher a score is, the more anxious behaviors there are. The second part is a depressive behavior scale, which the lowest score is 0, and the highest is 21, and the higher the score, the more depressive behaviors there are. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ActiGraphy | continuous between baseline and 12 weeks | Measures movement patterns during daily activities and exercise. This is measured in steps taken and movement sensors. The higher amount of steps and activity, the more that they are being active and doing exercise. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Exercise--Rock Steady Boxing Class Participants will be going twice a week to a Rock Steady Boxing class for an hour/class. Participants will be going to this class for a total of three months.
Exercise--Rock Steady Boxing class: Rock Steady Boxing is a class designed specifically for those with Parkinsonism and movement difficulty using explosive and fine tuned movements as well as cognitive learning skills. | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Exercise--Rock Steady Boxing Class |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 68.22 years STANDARD_DEVIATION 6.59 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 2 / 37 |
| serious Total, serious adverse events | 0 / 37 |
Outcome results
Primary
Change in Beta-Amyloid Levels
Using MRI/PET scans to measure change from baseline to followup of beta-amyloid levels
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Change in Beta-Amyloid Levels | 0.016675963 SUVr | Standard Deviation 0.037511718 |
Primary
Change in Hopkins Verbal Learning Test (HVLT) Scores
HVLT measures verbal learning skills and memory, highest score is 36 and lowest score is 0. The higher score demonstrates better recall/recognition abilities with verbal learning.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Change in Hopkins Verbal Learning Test (HVLT) Scores | HVLT | 1.67 score on a scale | Standard Deviation 3.83 |
| Exercise--Rock Steady Boxing Class | Change in Hopkins Verbal Learning Test (HVLT) Scores | HVLT Delayed Recall | 0.78 score on a scale | Standard Deviation 1.78 |
Primary
Change in Movement Disorder Society--Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS)
UPDRS measures ease of movement. Highest Score is 108, lowest score is 0. The higher the score, the more difficult movement is for patient.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Change in Movement Disorder Society--Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS) | 2.79 score on a scale | Standard Deviation 14.1 |
Primary
Freezing of Gait Questionnaire (FOG-Q)
Measures walking gait and how stable it is. Highest score is 24, lowest is 0. The higher the score, the worse walking gait is.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Freezing of Gait Questionnaire (FOG-Q) | 0.1052631578947 Units on a scale | Standard Deviation 0.6578362547106 |
Primary
Hospital Anxiety and Depression Scale (HADS)
The HADS measures anxious and depressive feelings in patients. There are 2 parts, Anxiety, where the lowest score would be a 0 and the highest is 21, and the higher a score is, the more anxious behaviors there are. The second part is a depressive behavior scale, which the lowest score is 0, and the highest is 21, and the higher the score, the more depressive behaviors there are.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Hospital Anxiety and Depression Scale (HADS) | HADS-A | -0.07 score on a scale | Standard Deviation 2.58 |
| Exercise--Rock Steady Boxing Class | Hospital Anxiety and Depression Scale (HADS) | HADS-D | -0.64 score on a scale | Standard Deviation 2.44 |
Primary
Letter Fluency (FAS)
FAS measures how many words a patient can list in a minute beginning with a certain letter (F, A, or S), relating to verbal learning and executive function. The lowest score is 0 words, and the more words listed in a minute beginning with each letter, the better executive functioning. FAS is a unitary neuropsychometric test composed of sub-tasks (F, A, S). The individual scores should not be / are not interpreted.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Letter Fluency (FAS) | 1.57 score on a scale | Standard Deviation 6.86 |
Primary
Mini-Balence Evaluation Systems Test (BESTest)
Mini-BESTest describes movement ability and balance in different scenarios. Highest score is 28, lowest score is 0. The higher the score, the better balance/movement in different conditions.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Mini-Balence Evaluation Systems Test (BESTest) | 4.00 score on a scale | Standard Deviation 3.64 |
Primary
Patient Recorded Outcomes Measurement Information System-Sleep Disturbance (PROMIS-Sleep)
The PROMIS measures sleep disturbance and impairment. The lowest score is an 8 and the highest is a 40. The higher the score, the worse sleep impairment or disturbance is.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Patient Recorded Outcomes Measurement Information System-Sleep Disturbance (PROMIS-Sleep) | PROMIS-SRI | -0.21 score on a scale | Standard Deviation 5.47 |
| Exercise--Rock Steady Boxing Class | Patient Recorded Outcomes Measurement Information System-Sleep Disturbance (PROMIS-Sleep) | PRMIS-SD | -1.18 score on a scale | Standard Deviation 5.62 |
Primary
Simon Task
The Simon task is another well-validated measure of inhibitory action control which has also been studied extensively in PD. This is a conflict task which measures the effect of interfering impulses on the ability to select a goal response. Scores are measured in % accuracy from 0-100, and reaction times from 0 ms and upward per item. The higher the accuracy and lower the reaction time, the better the inhibitory action control and executive functioning. The outcome we used is mean and standard deviation of reaction time (seconds) for items correctly responded to.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Simon Task | 1.2777777777777 seconds | Standard Deviation 5.3556518310984 |
Primary
Stroop Interference Task
The stroop interference task measures Measures completion time and number of errors, both corrected and not corrected, and total errors. The low and high scores are patient dependent upon performance, and the higher the scores, the more errors have been made and the worse executive functioning. The amount of time taken on the Stroop task also correlates to having worse executive functioning with a higher completion time.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Stroop Interference Task | Stroop-Color | 2.83 score on a scale | Standard Deviation 5.91 |
| Exercise--Rock Steady Boxing Class | Stroop Interference Task | Stroop-Word | 3.68 score on a scale | Standard Deviation 13.71 |
| Exercise--Rock Steady Boxing Class | Stroop Interference Task | Stroop-Color/Word | 3.38 score on a scale | Standard Deviation 5.75 |
Primary
Trail Making Test A&B (TMT)
TMT measures executive functioning and error detection. Measured with time to complete trails. Higher time to complete means more difficulty with executive functioning.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exercise--Rock Steady Boxing Class | Trail Making Test A&B (TMT) | TMT A | 3.94 score on a scale | Standard Deviation 24.99 |
| Exercise--Rock Steady Boxing Class | Trail Making Test A&B (TMT) | TMT B | 2.82 score on a scale | Standard Deviation 50.78 |
Secondary
ActiGraphy
Measures movement patterns during daily activities and exercise. This is measured in steps taken and movement sensors. The higher amount of steps and activity, the more that they are being active and doing exercise.
Time frame: continuous between baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exercise--Rock Steady Boxing Class | ActiGraphy | 8314.22 average step count | Standard Deviation 2904.98 |