Parkinson Disease
Conditions
Keywords
Parkinson Disease, Basal Ganglia Disease, Central Nervous System Diseases, Nervous System Diseases, Movement Disorders, Neurodegenerative Diseases, Brain Diseases
Brief summary
The purpose of this study is to learn more about the effects of exercise on patients who have been recently diagnosed with Parkinson's disease (PD). The investigators are going to test two levels of exercise (moderate to vigorous) against no exercise. The investigators think that exercise may reduce the symptoms the of PD, and the investigators hope to learn what level of exercise will offer the most benefit.
Detailed description
The overall objective of this study is to determine the futility or non-futility of conducting a randomized controlled trial to determine the effects of exercise on the progression of PD symptoms. The primary aim is to determine whether individuals with de novo Parkinson's disease (naïve to drug treatment) can achieve the randomly assigned levels of mean exercise intensity (60-65% HRmax or 80-85% HRmax) and adhere to the exercise protocol.
Interventions
BEHAVIORALModerate Exercise
Endurance exercise at 60 - 65% heart rate (HR) max,4x/wk for 6 months.
BEHAVIORALVigorous Exercise
Endurance exercise at 80-85% HR max, 4x/wk for 6 months.
BEHAVIORALNo Intervention
No-exercise control (i.e., usual care);
Sponsors
University of Illinois at Chicago
University of Pittsburgh
Rush University Medical Center
National Institute of Neurological Disorders and Stroke (NINDS)
Northwestern University
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of primary Parkinson's disease * In a Hoehn and Yahr stage less than stage III * Disease duration is less than 5 years * Not likely to require dopaminergic therapy within 6 months
Exclusion criteria
* Use of any PD medication within 60 days prior to the beginning the study, including levodopa, direct dopamine agonists, amantadine, Rasagiline (Azilect), Selegiline (Eldepryl), Artane (trihexyphenidyl). * Duration of previous use of medications for PD that exceeds 90 days * Expected to require dopaminergic therapy in the next 6 months * Poorly controlled or unstable cardiovascular disease * Uncontrolled hypertension * Hypo- or hyperthyroidism, abnormal liver function, abnormal renal function * Mild cognitive impairment (Montreal Cognitive Assessment score\<26/30) * Depression that precludes ability to exercise (Beck depression score\>13) * Disorders that interfere with ability to perform endurance exercises * Regular participation in vigorous endurance exercise * Evidence of serious arrhythmias or ischemic heart disease * Any clinically significant medical condition, psychiatric condition, drug or alcohol abuse, or laboratory abnormality that would, in the judgment of the investigators, interfere with the ability to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Average Maximum Heart Rate During Exercise as a Measure of Adherence to Exercise | 9 to 26 weeks | To test whether individuals with de novo Parkinson's disease (naïve to drug treatment) can achieve the randomly assigned levels of mean exercise intensity (60-65% average HRmax or 80-85% average HRmax) and adhere to the exercise protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 Month Change in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score | Baseline and 6 months | Participants were assessed at baseline and at 6 months on their UPDRS. If a participant initiated Parkinson disease medication prior to the 6 month assessment, the UPDRS score from the clinical visit assessment prior to this initiation was used as the score for the individual at 6 months. The change in the UPDRS motor score at 6 months was used as the measure for the futility component of the trial. The change at 6 months was measured as the 6 month value minus the baseline score. A positive change represents worsening of motor symptoms; 0 represents no change; negative values represent improvement. The minimum score on the UPDRS motor is 0 and the maximum is 108 at baseline and 6 months with higher scores representing worse motor symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Days of Exercise Per Week | 9 to 26 weeks | The number of days the participant exercised per week |
Countries
United States
Participant flow
Recruitment details
Prescreening by telephone and for patients in movement disorder clinics from May 2012 to November 2015.
Pre-assignment details
Screening included confirmation of Parkinson disease diagnosis, assessment of depression and cognition, testing for laboratory measures, and testing for blood pressure and echocardiogram responses to exercise during graded exercise. Once deemed eligible, baseline assessments were completed for disease and non-disease specific scales.
Participants by arm
| Arm | Count |
|---|---|
| Control Group Wait listed to moderate or vigorous exercise after 6 months of no exercise.
No Intervention: No-exercise control (i.e., usual care); | 40 |
| Vigorous Exercise Endurance exercise at 80-85% HR max, 4x/wk for 6 months.
Vigorous Exercise: Endurance exercise at 80-85% HR max, 4x/wk for 6 months. | 43 |
| Moderate Exercise Endurance exercise at 60-65% HR max, 4x/wk for 6 months.
Moderate Exercise: Endurance exercise at 60 - 65% heart rate (HR) max,4x/wk for 6 months. | 45 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 2 |
| Overall Study | Missing assessment | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Vigorous Exercise | Control Group | Moderate Exercise |
|---|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9 | 64 years STANDARD_DEVIATION 9 | 64 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants | 39 Participants | 39 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 0 Participants | 2 Participants |
| Hoehn and Yahr Stage Stage 1 | 33 Participants | 12 Participants | 8 Participants | 13 Participants |
| Hoehn and Yahr Stage Stage 2 | 95 Participants | 31 Participants | 32 Participants | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 115 Participants | 39 Participants | 36 Participants | 40 Participants |
| Sex: Female, Male Female | 55 Participants | 21 Participants | 16 Participants | 18 Participants |
| Sex: Female, Male Male | 73 Participants | 22 Participants | 24 Participants | 27 Participants |
| Total daily steps | 5306 steps per day STANDARD_DEVIATION 2856 | 5146 steps per day STANDARD_DEVIATION 3107 | 5005 steps per day STANDARD_DEVIATION 2987 | 5702 steps per day STANDARD_DEVIATION 2521 |
| Unified Parkinson Disease Rating Scale Part 3 Motor Evaluation | 17 units on a scale STANDARD_DEVIATION 7 | 17 units on a scale STANDARD_DEVIATION 7 | 17 units on a scale STANDARD_DEVIATION 7 | 16 units on a scale STANDARD_DEVIATION 7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 43 | 0 / 45 |
| other Total, other adverse events | 13 / 40 | 28 / 43 | 24 / 45 |
| serious Total, serious adverse events | 0 / 40 | 0 / 43 | 2 / 45 |
Outcome results
Primary
Percentage of Average Maximum Heart Rate During Exercise as a Measure of Adherence to Exercise
To test whether individuals with de novo Parkinson's disease (naïve to drug treatment) can achieve the randomly assigned levels of mean exercise intensity (60-65% average HRmax or 80-85% average HRmax) and adhere to the exercise protocol.
Time frame: 9 to 26 weeks
Population: Only for participants who contributed heart rate monitor data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vigorous Exercise | Percentage of Average Maximum Heart Rate During Exercise as a Measure of Adherence to Exercise | 80.3 percentage of maximum heart rate |
| Moderate Exercise | Percentage of Average Maximum Heart Rate During Exercise as a Measure of Adherence to Exercise | 65.9 percentage of maximum heart rate |
p-value: <0.000195% CI: [12, 16.6]t-test, 2 sided
Secondary
6 Month Change in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score
Participants were assessed at baseline and at 6 months on their UPDRS. If a participant initiated Parkinson disease medication prior to the 6 month assessment, the UPDRS score from the clinical visit assessment prior to this initiation was used as the score for the individual at 6 months. The change in the UPDRS motor score at 6 months was used as the measure for the futility component of the trial. The change at 6 months was measured as the 6 month value minus the baseline score. A positive change represents worsening of motor symptoms; 0 represents no change; negative values represent improvement. The minimum score on the UPDRS motor is 0 and the maximum is 108 at baseline and 6 months with higher scores representing worse motor symptoms.
Time frame: Baseline and 6 months
Population: Intention to treat; participants were analyzed in the group to which they were assigned. If a participant started medication, the UPDRS measure prior to initiating medication was used even if the 6 month data were not collected. Participants who did not start medications and were missing the 6 month assessment were not included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vigorous Exercise | 6 Month Change in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score | 3.2 units on the UPDRS Motor scale |
| Moderate Exercise | 6 Month Change in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score | 0.3 units on the UPDRS Motor scale |
| Moderate Exercise | 6 Month Change in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score | 2.0 units on the UPDRS Motor scale |
Comparison: The null hypothesis is that the vigorous exercise group warrants further investigation using a futility threshold of 3.5 compared to the control group (difference between the mean change in the control group and the mean change in the vigorous exercise group). The alternative hypothesis is that vigorous exercise does not warrant further investigation.p-value: 0.34t-test, 1 sided
Comparison: The null hypothesis is that the moderate exercise group warrants further investigation using a futility threshold of 3.5 compared to the control group (difference in the mean change between the control group and the moderate exercise group). The alternative hypothesis is that moderate exercise does not warrant further investigation .p-value: 0.03t-test, 1 sided
Other Pre-specified
Number of Days of Exercise Per Week
The number of days the participant exercised per week
Time frame: 9 to 26 weeks
Population: Participants were analyzed in the group to which they were assigned. Participants were not included if they did not start the intervention.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Vigorous Exercise | Number of Days of Exercise Per Week | 2.8 Number of days per week |
| Moderate Exercise | Number of Days of Exercise Per Week | 3.2 Number of days per week |
p-value: 0.1334t-test, 2 sided