Parkinson Disease
Conditions
Keywords
Exercise
Brief summary
Identification of an effective disease-modifying intervention (e.g. pharmaceutical, surgical or behavioral) is an unmet need in Parkinson's disease (PD). Increasing evidence indicates high intensity aerobic exercise is a candidate to alter PD progression. The primary aim of this study is to examine the disease-altering capabilities of a long-term, high-intensity aerobic exercise intervention. A multi-site pragmatic randomized controlled trial design has been selected. Individuals with PD will be randomized into 1) a home-based aerobic exercise program, or 2) a usual and customary care (UCC). Subjects in the home exercise group will receive an indoor stationary bicycle delivered to their home for a 12 month exercise period. Individuals in the UCC group will continue their current level of physical activity. Motor and non-motor assessments will be conducted at the main campus of the Cleveland Clinic or the University of Utah at enrollment, 6 months, and 12 months. Each assessment will last approximately one hour.
Detailed description
Overview of Experimental Design: The study is a randomized controlled clinical trial designed to examine the disease-altering capabilities of a 12 month aerobic exercise program for individuals with PD. A total of 252 individuals with PD will be randomized into 1) a home-based aerobic exercise program, or 2) a usual and customary care (UCC). Subjects in the home exercise group will receive a commercially available Peloton indoor stationary bicycle delivered to their home for a 12 month exercise period. Individuals in the UCC group will continue their current level of physical activity. Both groups will undergo a series of motor and non-motor assessments at enrollment, 6 months, and 12 months to measure disease progression of the 12 month period. Additionally, data will be used to develop a prognostic model to predict 12-month change in Movement Disorder Society - Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) for patients participating in a home-based high-intensity aerobic exercise program.
Interventions
OTHERHigh-Intensity Aerobic Exercise (AE)
The home-based exercise group will have a Peloton indoor cycle, heart rate monitor strap, and Garmin activity monitor to track daily activity levels delivered to the home. Participants will be asked to cycle 3x/week for 12 months on this bike with heart rate monitor at aerobic intensity 60-80% of heart rate reserve and target cadence 80-90 revolutions per minute. Study team members will telephone all participants biweekly for similar contact times between treatment groups. During these calls, a study team member reviews fall diary information, inquires about possible adverse events, and reviews participants' activity monitor wear times on the Garmin Connect website (https://connect.garmin.com). For those in the AE group, exercise recommendations, e.g., increase duration, cadence or heart rate, are given based on review of exercise session data on the Peloton portal (onepeloton.com). Compliance barriers or technical challenges with the activity monitor or exercise cycle are addressed.
Participants in this group will continue to receive their usual care. They will also receive activity monitors to monitor their daily activity levels, and telephone monitoring throughout the study. Study team members telephone all participants every 2 weeks for similar amounts of contact time between treatment groups. During the calls, a study team member of the reviews fall diary information, inquires about possible adverse events, and reviews participants' activity monitor wear times via the Garmin Connect website (https://connect.garmin.com).
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Utah
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) will be conducted by a consistent rater, blinded as to participant randomization group.
Intervention model description
252 mild to moderate PD patients will be randomized into a home cycling high-intensity aerobic exercise (AE) group or a Usual and Customary Care (UCC) group, asked to continue normal activity level and not initiate a formal cycling program during study participation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult with a diagnosis of idiopathic PD by a physician or physician extender * Hoehn and Yahr stage I-III * Demonstrate the ability to safely mount and dismount the Peloton stationary cycle * In-home wireless network (WiFi; required for Peloton system exercise data transmission)
Exclusion criteria
* Participation in pharmaceutical or behavioral disease modifying PD-related clinical trial or study * Diagnosis of dementia or any neurocognitive impairment that compromises one's ability to provide informed consent * Implanted deep brain stimulation electrodes * If the American College of Sports Medicine (ACSM) screen recommends medical clearance, the subject must obtain medical clearance by their health care provider prior to participation. * Any musculoskeletal issue that would limit one's ability to engage in exercise * Neurological disease other than Parkinson's disease (i.e. multiple sclerosis, stroke)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | Baseline, 6 months, 12 months | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination score, measured off medication. Range of scores is 0 to 132, with lower score indicating better motor function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | Baseline, 6 months, 12 months | The 10 Meter Walk Test (10MWT) evaluates gait speed similarly in separate trials with the participant instructed to walk at comfortable and fast pace, and velocity timed over the middle six meters. This outcome is the velocity (meters/second) with instructions to walk at a comfortable pace, performed off medication. Higher velocities indicate better motor function. |
| 10 Meter Walk Test (10MWT) Fast Pace Velocity | Baseline, 6 months, 12 months | The 10 Meter Walk Test (10MWT) evaluates gait speed similarly in separate trials with the participant instructed to walk at comfortable and fast pace, and velocity timed over the middle six meters. This outcome is the velocity (meters/second) with instructions to walk at a fast pace, performed off medication. Higher velocities indicate better motor function. |
| Timed Up and Go (TUG) Test Duration | Baseline, 6 months, 12 months | iPad-facilitated Timed Up and Go Test duration, measured off medication. The Timed Up & Go (TUG) Test requires an individual to (1) stand from a chair, (2) ambulate 3 m, (3) turn 180 degrees, (4) ambulate back to the chair, and (5) turn and sit. To perform an instrumented TUG, an Apple iPad is attached to the individual's waist (sacral level) via an adjustable belt. This outcome is the total time to complete this test, in seconds, measured off medication. Lower times indicate better motor function. |
| Timed Up and Go (TUG) Test Turning Velocity | Baseline, 6 months, 12 months | iPad-facilitated Timed Up and Go Test mean turning velocity, measured off medication. The Timed Up & Go (TUG) Test requires an individual to (1) stand from a chair, (2) ambulate 3 m, (3) turn 180 degrees, (4) ambulate back to the chair, and (5) turn and sit. To perform an instrumented TUG, an Apple iPad is attached to the individual's waist (sacral level) via an adjustable belt. This outcome is the mean velocity during performance of step (3), turn 180 degrees, in degrees/second, measured off medication. Higher turn velocities indicate better motor function. |
| Manual Dexterity Test Completion Time | Baseline, 6 months, 12 months | Manual Dexterity Test time to completion in seconds, measured off medication. This test is an electronic (iPad-based), modified version of the 9-hole peg test, where an individual is required to grasp, transfer, and release pegs into a 3×3 grid. Participants are asked to grasp and place pegs into holes, and then to return them to their starting locations, as rapidly as possible. Completion times for two repetitions conducted with each hand were averaged. Shorter completion times indicate better motor function. |
| Processing Speed Test Match Score | Baseline, 6 months, 12 months | The Processing Speed Test is a self-administered electronic (iPad) facilitated symbol-number matching task that is similar to the Symbol Digital Modalities Test. Participants are shown a table with numerical labels for 9 disparate symbols, and a second table with a row of such symbols and a blank row beneath it, and asked to complete the second table with the numbers from the first table corresponding to each symbol in the second. When the table is completed, additional tables are shown. The response recorded is the number of correct matches of symbols with numbers in 120 seconds, measured off medication. Higher values indicate faster neural processing. |
| Trail Making Test (TMT) B to A Duration Ratio | Baseline, 6 months, 12 months | Participants completed iPad versions of Trail Making Tests A and B (TMT A and B, respectively), with durations in seconds recorded for each. TMT A, considered predominantly a motor task, requires the participant to use a stylus to connect dots in ascending numeric order (1-2-3-4 . . . ). The TMT B, requires the participant to connect dots in an ascending and alternating alpha and numeric order (1-A-2-B . . . .). The total times to complete each of the TMT A and B tasks are automatically recorded by the iPad. This outcome is the (unitless) ratio of the duration to complete Trail Making Test B to the duration to complete Trail Making Test A, reflecting the cognitive burden of visual attention and set-switching, measured off medication. Higher values reflect greater relative burden of the additional cognitive component. |
| Visual Memory Test Symbol Recall Score | Baseline, 6 months, 12 months | Electronics-based test of episodic memory performed on an iPad, reported as number of correctly recalled symbols arrayed on a grid, with values ranging from 0 to 70 and higher numbers reflective of better memory, measured off medication. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Intensity Aerobic Exercise Group Mild to moderate Parkinson's disease patients receiving a Peloton indoor cycle and a heart rate monitor strap delivered to the home, and asked to cycle 3x/week for 12 months with goal of progressing to 45 minute sessions with the heart rate monitor at an aerobic intensity between 60-80% of heart rate reserve with a target cadence between 80-90 revolutions per minute (RPMs). Participants also receive and are asked to wear activity monitors throughout the day to monitor daily. activity levels. Participants also receive biweekly telephone calls to review electronic activity monitoring and exercise data, monitor falls and adverse events, and for guidance on progressing their cycling exercise sessions. See Alberts JL et al., Physical Therapy, 2021;101:1-10. | 129 |
| Usual and Customary Care Group Mild to moderate Parkinson's disease patients receiving no active exercise intervention through the research. These participants continued to receive usual and customary care (UCC) for their Parkinson's disease during the 12 month follow-up period. Participants receive and are asked to wear activity monitors throughout the day to monitor daily activity levels, and not to commence a cycling exercise program for the duration of the 12 month follow-up period. Participants also receive biweekly telephone calls to review electronic activity monitoring data, monitor falls and adverse events, and to provide them similar contact time as for the active exercise group. | 127 |
| Total | 256 |
Baseline characteristics
| Characteristic | High-Intensity Aerobic Exercise Group | Usual and Customary Care Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 59 Participants | 74 Participants | 133 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 53 Participants | 123 Participants |
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.6 | 65.2 years STANDARD_DEVIATION 8.2 | 64.2 years STANDARD_DEVIATION 8.5 |
| Clinical Site Cleveland Clinic | 66 Participants | 65 Participants | 131 Participants |
| Clinical Site University of Utah | 63 Participants | 62 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 125 Participants | 125 Participants | 250 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Movement Disorder Society-Unified Parkinson's Disease Rating Scale (Motor Examination) | 38.5 units on a scale STANDARD_DEVIATION 15.6 | 36.9 units on a scale STANDARD_DEVIATION 14.2 | 37.7 units on a scale STANDARD_DEVIATION 14.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 123 Participants | 121 Participants | 244 Participants |
| Region of Enrollment United States | 129 participants | 127 participants | 256 participants |
| Sex/Gender, Customized Female | 42 Participants | 43 Participants | 85 Participants |
| Sex/Gender, Customized Male | 86 Participants | 84 Participants | 170 Participants |
| Sex/Gender, Customized Sex/Prefer not to answer | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 127 |
| other Total, other adverse events | 27 / 129 | 0 / 127 |
| serious Total, serious adverse events | 10 / 129 | 15 / 127 |
Outcome results
Primary
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score
Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination score, measured off medication. Range of scores is 0 to 132, with lower score indicating better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Means and standard deviations are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic modeling results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | Baseline | 38.5 Score on a scale | Standard Deviation 15.6 |
| Aerobic Exercise Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | 6 months | 35.9 Score on a scale | Standard Deviation 14.1 |
| Aerobic Exercise Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | 12 months | 37.1 Score on a scale | Standard Deviation 13.7 |
| Usual and Customary Care Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | Baseline | 36.9 Score on a scale | Standard Deviation 14.2 |
| Usual and Customary Care Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | 6 months | 38.8 Score on a scale | Standard Deviation 15.7 |
| Usual and Customary Care Group | Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III: Motor Examination Score | 12 months | 40.5 Score on a scale | Standard Deviation 16.4 |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and AR(1) covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX.p-value: <0.000195% CI: [-5.4, -1.85]Mixed Models Analysis
Secondary
10 Meter Walk Test (10MWT) Comfortable Pace Velocity
The 10 Meter Walk Test (10MWT) evaluates gait speed similarly in separate trials with the participant instructed to walk at comfortable and fast pace, and velocity timed over the middle six meters. This outcome is the velocity (meters/second) with instructions to walk at a comfortable pace, performed off medication. Higher velocities indicate better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Medians and interquartile ranges are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | Baseline | 1.22 meters/second |
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | 6 months | 1.23 meters/second |
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | 12 months | 1.24 meters/second |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | Baseline | 1.26 meters/second |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | 6 months | 1.25 meters/second |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Comfortable Pace Velocity | 12 months | 1.24 meters/second |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, test velocity was squared ((meters/second)\^2) for modeling. Study sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.04395% CI: [3.1, 21.32]Mixed Models Analysis
Secondary
10 Meter Walk Test (10MWT) Fast Pace Velocity
The 10 Meter Walk Test (10MWT) evaluates gait speed similarly in separate trials with the participant instructed to walk at comfortable and fast pace, and velocity timed over the middle six meters. This outcome is the velocity (meters/second) with instructions to walk at a fast pace, performed off medication. Higher velocities indicate better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Means and standard deviations are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | Baseline | 1.66 meters/second | Standard Deviation 0.34 |
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | 6 months | 1.67 meters/second | Standard Deviation 0.35 |
| Aerobic Exercise Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | 12 months | 1.67 meters/second | Standard Deviation 0.36 |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | Baseline | 1.67 meters/second | Standard Deviation 0.33 |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | 6 months | 1.64 meters/second | Standard Deviation 0.36 |
| Usual and Customary Care Group | 10 Meter Walk Test (10MWT) Fast Pace Velocity | 12 months | 1.64 meters/second | Standard Deviation 0.39 |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and heterogeneous compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX.p-value: 0.4895% CI: [-2.1, 8.42]Mixed Models Analysis
Secondary
Manual Dexterity Test Completion Time
Manual Dexterity Test time to completion in seconds, measured off medication. This test is an electronic (iPad-based), modified version of the 9-hole peg test, where an individual is required to grasp, transfer, and release pegs into a 3×3 grid. Participants are asked to grasp and place pegs into holes, and then to return them to their starting locations, as rapidly as possible. Completion times for two repetitions conducted with each hand were averaged. Shorter completion times indicate better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Medians and interquartile ranges are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | Manual Dexterity Test Completion Time | Baseline | 26.4 Time (seconds) to completion |
| Aerobic Exercise Group | Manual Dexterity Test Completion Time | 6 months | 26.4 Time (seconds) to completion |
| Aerobic Exercise Group | Manual Dexterity Test Completion Time | 12 months | 26.1 Time (seconds) to completion |
| Usual and Customary Care Group | Manual Dexterity Test Completion Time | 12 months | 26.5 Time (seconds) to completion |
| Usual and Customary Care Group | Manual Dexterity Test Completion Time | Baseline | 26.1 Time (seconds) to completion |
| Usual and Customary Care Group | Manual Dexterity Test Completion Time | 6 months | 26.0 Time (seconds) to completion |
Comparison: Linear mixed model for baseline, 6 and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, test duration was transformed for modeling to peg transfers/second (18/seconds). Sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.7295% CI: [-23.68, 16.45]Mixed Models Analysis
Secondary
Processing Speed Test Match Score
The Processing Speed Test is a self-administered electronic (iPad) facilitated symbol-number matching task that is similar to the Symbol Digital Modalities Test. Participants are shown a table with numerical labels for 9 disparate symbols, and a second table with a row of such symbols and a blank row beneath it, and asked to complete the second table with the numbers from the first table corresponding to each symbol in the second. When the table is completed, additional tables are shown. The response recorded is the number of correct matches of symbols with numbers in 120 seconds, measured off medication. Higher values indicate faster neural processing.
Time frame: Baseline, 6 months, 12 months
Population: Medians and interquartile ranges are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | Processing Speed Test Match Score | Baseline | 45.0 Correct symbol/number matches |
| Aerobic Exercise Group | Processing Speed Test Match Score | 6 month | 46.0 Correct symbol/number matches |
| Aerobic Exercise Group | Processing Speed Test Match Score | 12 month | 44.0 Correct symbol/number matches |
| Usual and Customary Care Group | Processing Speed Test Match Score | Baseline | 44.0 Correct symbol/number matches |
| Usual and Customary Care Group | Processing Speed Test Match Score | 6 month | 45.0 Correct symbol/number matches |
| Usual and Customary Care Group | Processing Speed Test Match Score | 12 month | 45.0 Correct symbol/number matches |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and heterogeneous compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, test duration was squared (matches\^2) for analysis. Study sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.4895% CI: [-232.41, 38.6]Mixed Models Analysis
Secondary
Timed Up and Go (TUG) Test Duration
iPad-facilitated Timed Up and Go Test duration, measured off medication. The Timed Up & Go (TUG) Test requires an individual to (1) stand from a chair, (2) ambulate 3 m, (3) turn 180 degrees, (4) ambulate back to the chair, and (5) turn and sit. To perform an instrumented TUG, an Apple iPad is attached to the individual's waist (sacral level) via an adjustable belt. This outcome is the total time to complete this test, in seconds, measured off medication. Lower times indicate better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Medians and interquartile ranges are reported for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic modeling results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Duration | Baseline | 9.9 seconds |
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Duration | 6 months | 10.4 seconds |
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Duration | 12 months | 9.9 seconds |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Duration | Baseline | 10.0 seconds |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Duration | 6 months | 10.3 seconds |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Duration | 12 months | 10.3 seconds |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, test duration was inverted to TUG completions/second. Sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.1695% CI: [0.2, 7.89]Mixed Models Analysis
Secondary
Timed Up and Go (TUG) Test Turning Velocity
iPad-facilitated Timed Up and Go Test mean turning velocity, measured off medication. The Timed Up & Go (TUG) Test requires an individual to (1) stand from a chair, (2) ambulate 3 m, (3) turn 180 degrees, (4) ambulate back to the chair, and (5) turn and sit. To perform an instrumented TUG, an Apple iPad is attached to the individual's waist (sacral level) via an adjustable belt. This outcome is the mean velocity during performance of step (3), turn 180 degrees, in degrees/second, measured off medication. Higher turn velocities indicate better motor function.
Time frame: Baseline, 6 months, 12 months
Population: Means and standard deviations are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Turning Velocity | Baseline | 77.3 degrees/second | Standard Deviation 19 |
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Turning Velocity | 6 months | 76.3 degrees/second | Standard Deviation 18 |
| Aerobic Exercise Group | Timed Up and Go (TUG) Test Turning Velocity | 12 months | 77.1 degrees/second | Standard Deviation 18.5 |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Turning Velocity | Baseline | 78.5 degrees/second | Standard Deviation 16.6 |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Turning Velocity | 6 months | 74.5 degrees/second | Standard Deviation 18.6 |
| Usual and Customary Care Group | Timed Up and Go (TUG) Test Turning Velocity | 12 months | 76.8 degrees/second | Standard Deviation 18.9 |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. Study sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.6995% CI: [-1.17, 4.88]Mixed Models Analysis
Secondary
Trail Making Test (TMT) B to A Duration Ratio
Participants completed iPad versions of Trail Making Tests A and B (TMT A and B, respectively), with durations in seconds recorded for each. TMT A, considered predominantly a motor task, requires the participant to use a stylus to connect dots in ascending numeric order (1-2-3-4 . . . ). The TMT B, requires the participant to connect dots in an ascending and alternating alpha and numeric order (1-A-2-B . . . .). The total times to complete each of the TMT A and B tasks are automatically recorded by the iPad. This outcome is the (unitless) ratio of the duration to complete Trail Making Test B to the duration to complete Trail Making Test A, reflecting the cognitive burden of visual attention and set-switching, measured off medication. Higher values reflect greater relative burden of the additional cognitive component.
Time frame: Baseline, 6 months, 12 months
Population: Medians and interquartile ranges are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | Trail Making Test (TMT) B to A Duration Ratio | Baseline | 1.58 unitless ratio |
| Aerobic Exercise Group | Trail Making Test (TMT) B to A Duration Ratio | 6 months | 1.51 unitless ratio |
| Aerobic Exercise Group | Trail Making Test (TMT) B to A Duration Ratio | 12 months | 1.44 unitless ratio |
| Usual and Customary Care Group | Trail Making Test (TMT) B to A Duration Ratio | Baseline | 1.55 unitless ratio |
| Usual and Customary Care Group | Trail Making Test (TMT) B to A Duration Ratio | 6 months | 1.52 unitless ratio |
| Usual and Customary Care Group | Trail Making Test (TMT) B to A Duration Ratio | 12 months | 1.52 unitless ratio |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, the ratios were transformed to their natural logarithms for modeling. Study sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 195% CI: [-15.31, 8.46]Mixed Models Analysis
Secondary
Visual Memory Test Symbol Recall Score
Electronics-based test of episodic memory performed on an iPad, reported as number of correctly recalled symbols arrayed on a grid, with values ranging from 0 to 70 and higher numbers reflective of better memory, measured off medication.
Time frame: Baseline, 6 months, 12 months
Population: Medians and quartiles are for the observed data, without imputation of missing data due to baseline or subsequent dropouts. Analytic modeling results reported below are based on the full intention-to-treat population, with missing data multiply-imputed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Aerobic Exercise Group | Visual Memory Test Symbol Recall Score | Baseline | 49 Number correct |
| Aerobic Exercise Group | Visual Memory Test Symbol Recall Score | 6 month | 56 Number correct |
| Aerobic Exercise Group | Visual Memory Test Symbol Recall Score | 12 month | 57.5 Number correct |
| Usual and Customary Care Group | Visual Memory Test Symbol Recall Score | Baseline | 48 Number correct |
| Usual and Customary Care Group | Visual Memory Test Symbol Recall Score | 6 month | 54 Number correct |
| Usual and Customary Care Group | Visual Memory Test Symbol Recall Score | 12 month | 52 Number correct |
Comparison: Linear mixed model for baseline, 6 month, and 12 month data, with fixed effects of clinical site, treatment, and linear time nested in treatment arm, and compound symmetry covariance structure, fit by residual pseudolikelihood maximization (RSPL) in SAS PROC GLIMMIX. To reduce skew and better meet modeling assumptions, the score was squared for statistical modeling. Sample size was based on the primary outcome, and power was not calculated for this and other outcomes.p-value: 0.9195% CI: [-2.58, 2.91]Mixed Models Analysis