Stroke
Conditions
Keywords
Rehabilitation, Locomotion, Aerobic, Intensity, Dosing
Brief summary
The objective of this study is to determine the optimal training intensity and the minimum training duration needed to maximize immediate improvements in walking capacity in chronic stroke. A single-blind, phase II, 3-site randomized controlled trial has been planned. Fifty persons \>6 months post stroke will randomize to either moderate-intensity aerobic locomotor training or high-intensity interval locomotor training; each for 45 minutes, 3x/week for up to 36 total sessions over approximately 12 weeks. Clinical measures of walking function, aerobic fitness, daily walking activity and quality of life will be assessed at baseline (PRE) and after 4, 8 and 12 weeks of training (POST-4WK, POST-8WK, POST-12WK).
Interventions
BEHAVIORALModerate-Intensity Aerobic Training
Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve.
BEHAVIORALHigh-Intensity Interval Training
Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve.
Sponsors
University of Delaware
University of Kansas Medical Center
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Cincinnati
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
1. Age 40-80 years at time of consenting 2. Single stroke for which participant sought treatment, 6 months to 5 years prior to consent date 3. Walking speed \<1.0 m/s on the 10-meter walk test 4. Able to walk 10m over ground with assistive devices as needed and no continuous physical assistance from another person (guarding and intermittent assistance for loss of balance allowed) 5. Able to walk at least 3 minutes on the treadmill at ≥0.13m/s (0.3 mph) 6. Stable cardiovascular condition (AHA class B, allowing for aerobic capacity \<6 metabolic equivalents) 7. Able to communicate with investigators, follow a 2-step command and correctly answer consent comprehension questions
Exclusion criteria
1. Exercise testing uninterpretable for ischemia or arrhythmia (e.g. resting ECG abnormality that makes exercise ECG uninterpretable for ischemia and no other clinical testing from the past year available to rule out) 2. Evidence of significant arrhythmia or myocardial ischemia on treadmill ECG graded exercise test in the absence of recent (past year) more definitive clinical testing (e.g. stress nuclear imaging) with negative result 3. Hospitalization for cardiac or pulmonary disease within past 3 months 4. Implanted pacemaker or defibrillator 5. Significant ataxia or neglect (score of 2 on NIH stroke scale item 7 or 11) 6. Severe lower limb spasticity (Ashworth \>2) 7. Recent history (\<3 months) of illicit drug or alcohol abuse or significant mental illness 8. Major post-stroke depression (Patient Health Questionnaire \[PHQ-9\] ≥ 10) in the absence of depression management by a health care provider 9. Currently participating in physical therapy or another interventional study 10. Recent botulinum toxin injection to the paretic lower limb (\<3 months) or planning to have lower limb botulinum toxin injection in the next 4 months 11. Foot drop or lower limb joint instability without adequate stabilizing device, as assessed by a physical therapist 12. Clinically significant neurologic disorder other than stroke or unable to walk outside the home prior to stroke 13. Other significant medical condition likely to limit improvement or jeopardize safety as assessed by a physical therapist (e.g. joint contracture, gait limited by pain) 14. Pregnancy 15. Previous exposure to fast treadmill walking (\>3 cumulative hours) during clinical or research therapy in the past year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six-Minute Walk Test Distance | Change Six-Minute Walk Test Distance from Baseline to 4 Weeks | Total distance walked in 6 minutes in meters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comfortable Gait Speed | Change from Baseline to 4 Weeks | From 10-meter walk test, in meters per second |
| Fast Gait Speed | Change from Baseline to 4 Weeks | From 10-meter walk test, in meters per second |
| Aerobic Fitness | Change from Baseline to 4 Weeks | Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute |
| PROMIS-Fatigue Scale | Change from Baseline to 4 Weeks | The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale is an 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total raw score is calculated by summing the scores for each item. The raw score is then translated into a T-score based on normative data. The T-score is a standardized score with a mean of 50 and a standard deviation of 10 for the U.S. general population, so a T-score of 60 (for example) would represent one SD higher (worse) fatigue than the average American. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exercise Capacity | Change from Baseline to 4 Weeks | Time to exhaustion during treadmill graded exercise test, recorded in minutes |
| Daily Walking Activity | Change from Baseline to 4 Weeks | Mean daily step count recorded with activity monitor, recorded as steps per day |
| Peak Oxygen Consumption Rate | Change from Baseline to 4 Weeks | Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute |
| Metabolic Cost of Gait | Change from Baseline to 4 Weeks | Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter |
| EuroQol 5D-5L (EQ-5D-5L) | Change from Baseline to 4 Weeks | A 5-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total misery score was calculated by summing the scores for each item (min 5, max 25). |
| Activities-specific Balance Confidence Scale | Change from Baseline to 4 Weeks | A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score from 0-100 is calculated by averaging the scores for each item. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High-Intensity Interval Training High-Intensity Interval Training: Overground and treadmill walking with 30 second bursts at maximum speed alternated with 30-60 second passive recovery periods. Intended to achieve a target average heart rate above 60% heart rate reserve. | 27 |
| Moderate-Intensity Aerobic Training Moderate-Intensity Aerobic Training: Overground and treadmill walking with speed continuously adjusted to maintain a target heart rate of 40 +/- 5% heart rate reserve, progressing up to 55 +/- 5% heart rate reserve. | 28 |
| Total | 55 |
Baseline characteristics
| Characteristic | Total | Moderate-Intensity Aerobic Training | High-Intensity Interval Training |
|---|---|---|---|
| 6-minute walk test distance | 239 meters STANDARD_DEVIATION 132 | 230 meters STANDARD_DEVIATION 130 | 248 meters STANDARD_DEVIATION 136 |
| Age, Continuous | 62.6 years STANDARD_DEVIATION 9.9 | 61.5 years STANDARD_DEVIATION 9.9 | 63.8 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 54 Participants | 28 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 40 Participants | 17 Participants | 23 Participants |
| Region of Enrollment United States | 55 participants | 28 participants | 27 participants |
| Self-selected gait speed | 0.63 meters/second STANDARD_DEVIATION 0.31 | 0.62 meters/second STANDARD_DEVIATION 0.33 | 0.65 meters/second STANDARD_DEVIATION 0.29 |
| Sex: Female, Male Female | 19 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 36 Participants | 20 Participants | 16 Participants |
| Stroke chronicity | 2.5 years STANDARD_DEVIATION 1.3 | 2.2 years STANDARD_DEVIATION 1.2 | 2.7 years STANDARD_DEVIATION 1.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 13 / 27 | 10 / 28 |
| serious Total, serious adverse events | 1 / 27 | 3 / 28 |
Outcome results
Primary
Six-Minute Walk Test Distance
Total distance walked in 6 minutes in meters
Time frame: Change Six-Minute Walk Test Distance from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Six-Minute Walk Test Distance | 71 meters |
| Moderate-Intensity Aerobic Training | Six-Minute Walk Test Distance | 27 meters |
Primary
Six-Minute Walk Test Distance
Total distance walked in 6 minutes in meters
Time frame: Change Six-Minute Walk Test Distance from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Six-Minute Walk Test Distance | 27 meters |
| Moderate-Intensity Aerobic Training | Six-Minute Walk Test Distance | 12 meters |
Primary
Six-Minute Walk Test Distance
Total distance walked in 6 minutes in meters
Time frame: Change Six-Minute Walk Test Distance from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Six-Minute Walk Test Distance | 58 meters |
| Moderate-Intensity Aerobic Training | Six-Minute Walk Test Distance | 29 meters |
Secondary
Aerobic Fitness
Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Aerobic Fitness | 1.3 mL/kg/min |
| Moderate-Intensity Aerobic Training | Aerobic Fitness | 0.4 mL/kg/min |
Secondary
Aerobic Fitness
Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Aerobic Fitness | 2.0 mL/kg/min |
| Moderate-Intensity Aerobic Training | Aerobic Fitness | 1.7 mL/kg/min |
Secondary
Aerobic Fitness
Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Aerobic Fitness | 1.9 mL/kg/min |
| Moderate-Intensity Aerobic Training | Aerobic Fitness | 1.4 mL/kg/min |
Secondary
Comfortable Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Comfortable Gait Speed | 0.19 m/s |
| Moderate-Intensity Aerobic Training | Comfortable Gait Speed | 0.06 m/s |
Secondary
Comfortable Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Comfortable Gait Speed | 0.14 m/s |
| Moderate-Intensity Aerobic Training | Comfortable Gait Speed | 0.06 m/s |
Secondary
Comfortable Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Comfortable Gait Speed | 0.11 m/s |
| Moderate-Intensity Aerobic Training | Comfortable Gait Speed | 0.02 m/s |
Secondary
Fast Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Fast Gait Speed | 0.24 m/s |
| Moderate-Intensity Aerobic Training | Fast Gait Speed | 0.09 m/s |
Secondary
Fast Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Fast Gait Speed | 0.22 m/s |
| Moderate-Intensity Aerobic Training | Fast Gait Speed | 0.01 m/s |
Secondary
Fast Gait Speed
From 10-meter walk test, in meters per second
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Fast Gait Speed | 0.28 m/s |
| Moderate-Intensity Aerobic Training | Fast Gait Speed | 0.09 m/s |
Secondary
PROMIS-Fatigue Scale
The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale is an 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total raw score is calculated by summing the scores for each item. The raw score is then translated into a T-score based on normative data. The T-score is a standardized score with a mean of 50 and a standard deviation of 10 for the U.S. general population, so a T-score of 60 (for example) would represent one SD higher (worse) fatigue than the average American.
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | PROMIS-Fatigue Scale | -1.7 T score |
| Moderate-Intensity Aerobic Training | PROMIS-Fatigue Scale | 0.0 T score |
Secondary
PROMIS-Fatigue Scale
The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale is an 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total raw score is calculated by summing the scores for each item. The raw score is then translated into a T-score based on normative data. The T-score is a standardized score with a mean of 50 and a standard deviation of 10 for the U.S. general population, so a T-score of 60 (for example) would represent one SD higher (worse) fatigue than the average American.
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | PROMIS-Fatigue Scale | -3.0 T score |
| Moderate-Intensity Aerobic Training | PROMIS-Fatigue Scale | 1.0 T score |
Secondary
PROMIS-Fatigue Scale
The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale is an 8-item self-report questionnaire about symptoms of fatigue. Each item is rated from 1-5, where higher scores indicate greater fatigue. A total raw score is calculated by summing the scores for each item. The raw score is then translated into a T-score based on normative data. The T-score is a standardized score with a mean of 50 and a standard deviation of 10 for the U.S. general population, so a T-score of 60 (for example) would represent one SD higher (worse) fatigue than the average American.
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | PROMIS-Fatigue Scale | -1.1 T score |
| Moderate-Intensity Aerobic Training | PROMIS-Fatigue Scale | -0.1 T score |
Other Pre-specified
Activities-specific Balance Confidence Scale
A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score from 0-100 is calculated by averaging the scores for each item.
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Activities-specific Balance Confidence Scale | 1.6 score |
| Moderate-Intensity Aerobic Training | Activities-specific Balance Confidence Scale | -1.8 score |
Other Pre-specified
Activities-specific Balance Confidence Scale
A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score from 0-100 is calculated by averaging the scores for each item.
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Activities-specific Balance Confidence Scale | 2.5 score |
| Moderate-Intensity Aerobic Training | Activities-specific Balance Confidence Scale | 0.6 score |
Other Pre-specified
Activities-specific Balance Confidence Scale
A 16-item questionnaire that asks participants to rate their balance confidence during everyday tasks, as a percentage from 0-100%, where higher scores indicate greater balance self-efficacy. A total score from 0-100 is calculated by averaging the scores for each item.
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Activities-specific Balance Confidence Scale | -2.7 score |
| Moderate-Intensity Aerobic Training | Activities-specific Balance Confidence Scale | -4.6 score |
Other Pre-specified
Daily Walking Activity
Mean daily step count recorded with activity monitor, recorded as steps per day
Time frame: Change from Baseline to 12 Weeks
Population: Results are from a modified intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Four participants (2 in the HIT group and 2 in the MAT group) had to be excluded because they had no valid days of step data collected outside of study visits. Other missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Daily Walking Activity | 65 steps/day |
| Moderate-Intensity Aerobic Training | Daily Walking Activity | 267 steps/day |
Other Pre-specified
Daily Walking Activity
Mean daily step count recorded with activity monitor, recorded as steps per day
Time frame: Change from Baseline to 4 Weeks
Population: Results are from a modified intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Four participants (2 in the HIT group and 2 in the MAT group) had to be excluded because they had no valid days of step data collected outside of study visits. Other missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Daily Walking Activity | -56 steps/day |
| Moderate-Intensity Aerobic Training | Daily Walking Activity | -102 steps/day |
Other Pre-specified
Daily Walking Activity
Mean daily step count recorded with activity monitor, recorded as steps per day
Time frame: Change from Baseline to 8 Weeks
Population: Results are from a modified intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Four participants (2 in the HIT group and 2 in the MAT group) had to be excluded because they had no valid days of step data collected outside of study visits. Other missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Daily Walking Activity | -299 steps/day |
| Moderate-Intensity Aerobic Training | Daily Walking Activity | 359 steps/day |
Other Pre-specified
EuroQol 5D-5L (EQ-5D-5L)
A 5-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total misery score was calculated by summing the scores for each item (min 5, max 25).
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | EuroQol 5D-5L (EQ-5D-5L) | -0.9 score |
| Moderate-Intensity Aerobic Training | EuroQol 5D-5L (EQ-5D-5L) | -0.2 score |
Other Pre-specified
EuroQol 5D-5L (EQ-5D-5L)
A 5-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total misery score was calculated by summing the scores for each item (min 5, max 25).
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | EuroQol 5D-5L (EQ-5D-5L) | -0.1 score |
| Moderate-Intensity Aerobic Training | EuroQol 5D-5L (EQ-5D-5L) | -0.6 score |
Other Pre-specified
EuroQol 5D-5L (EQ-5D-5L)
A 5-item questionnaire about quality of life, including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item is scored from 1 to 5, where lower scores indicate greater quality of life. A total misery score was calculated by summing the scores for each item (min 5, max 25).
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | EuroQol 5D-5L (EQ-5D-5L) | -0.6 score |
| Moderate-Intensity Aerobic Training | EuroQol 5D-5L (EQ-5D-5L) | -0.4 score |
Other Pre-specified
Exercise Capacity
Time to exhaustion during treadmill graded exercise test, recorded in minutes
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Exercise Capacity | 2.5 minutes |
| Moderate-Intensity Aerobic Training | Exercise Capacity | 1.6 minutes |
Other Pre-specified
Exercise Capacity
Time to exhaustion during treadmill graded exercise test, recorded in minutes
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Exercise Capacity | 3.3 minutes |
| Moderate-Intensity Aerobic Training | Exercise Capacity | 2.2 minutes |
Other Pre-specified
Exercise Capacity
Time to exhaustion during treadmill graded exercise test, recorded in minutes
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Exercise Capacity | 1.8 minutes |
| Moderate-Intensity Aerobic Training | Exercise Capacity | 0.6 minutes |
Other Pre-specified
Metabolic Cost of Gait
Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Metabolic Cost of Gait | -0.10 mL/kg/m |
| Moderate-Intensity Aerobic Training | Metabolic Cost of Gait | -0.08 mL/kg/m |
Other Pre-specified
Metabolic Cost of Gait
Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Metabolic Cost of Gait | -0.08 mL/kg/m |
| Moderate-Intensity Aerobic Training | Metabolic Cost of Gait | -0.05 mL/kg/m |
Other Pre-specified
Metabolic Cost of Gait
Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Metabolic Cost of Gait | -0.12 mL/kg/m |
| Moderate-Intensity Aerobic Training | Metabolic Cost of Gait | -0.11 mL/kg/m |
Other Pre-specified
Peak Oxygen Consumption Rate
Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 12 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Peak Oxygen Consumption Rate | 2.5 mL/kg/min |
| Moderate-Intensity Aerobic Training | Peak Oxygen Consumption Rate | 1.5 mL/kg/min |
Other Pre-specified
Peak Oxygen Consumption Rate
Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 4 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Peak Oxygen Consumption Rate | 1.5 mL/kg/min |
| Moderate-Intensity Aerobic Training | Peak Oxygen Consumption Rate | 0.2 mL/kg/min |
Other Pre-specified
Peak Oxygen Consumption Rate
Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute
Time frame: Change from Baseline to 8 Weeks
Population: Results are from an intent-to-treat analysis using a linear mixed effects model that included all available time points (Baseline, 4-week, 8-week and 12-week) for all randomized participants and estimated contrasts for change from baseline to each time point. Missing data were handled with the maximum likelihood method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| High-Intensity Interval Training | Peak Oxygen Consumption Rate | 2.1 mL/kg/min |
| Moderate-Intensity Aerobic Training | Peak Oxygen Consumption Rate | 1.5 mL/kg/min |