Trial Outcomes & Findings for Moderate-Intensity Exercise Versus High-Intensity Interval Training to Recover Walking Post-Stroke (NCT NCT03760016)

NCT ID: NCT03760016

Last Updated: 2025-03-26

Results Overview

Total distance walked in 6 minutes in meters

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 55 participants
• Primary outcome timeframe: Change Six-Minute Walk Test Distance from Baseline to 4 Weeks
• Results posted on: 2025-03-26

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	27	28
Overall Study Completed 4-week Testing	26	27
Overall Study Completed 8-week Testing	23	24
Overall Study COMPLETED	19	23
Overall Study NOT COMPLETED	8	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Moderate-Intensity Exercise Versus High-Intensity Interval Training to Recover Walking Post-Stroke

Baseline characteristics by cohort

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.	Total n=55 Participants Total of all reporting groups
Age, Continuous	63.8 years STANDARD_DEVIATION 9.9 • n=5 Participants	61.5 years STANDARD_DEVIATION 9.9 • n=7 Participants	62.6 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	20 Participants n=7 Participants	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants	28 participants n=7 Participants	55 participants n=5 Participants
Stroke chronicity	2.7 years STANDARD_DEVIATION 1.4 • n=5 Participants	2.2 years STANDARD_DEVIATION 1.2 • n=7 Participants	2.5 years STANDARD_DEVIATION 1.3 • n=5 Participants
Self-selected gait speed	0.65 meters/second STANDARD_DEVIATION 0.29 • n=5 Participants	0.62 meters/second STANDARD_DEVIATION 0.33 • n=7 Participants	0.63 meters/second STANDARD_DEVIATION 0.31 • n=5 Participants
6-minute walk test distance	248 meters STANDARD_DEVIATION 136 • n=5 Participants	230 meters STANDARD_DEVIATION 130 • n=7 Participants	239 meters STANDARD_DEVIATION 132 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Total distance walked in 6 minutes in meters

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Six-Minute Walk Test Distance	27 meters Interval 6.0 to 48.0	12 meters Interval -9.0 to 33.0

PRIMARY outcome

Timeframe: 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.

Total distance walked in 6 minutes in meters

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Six-Minute Walk Test Distance	58 meters Interval 39.0 to 76.0	29 meters Interval 9.0 to 48.0

PRIMARY outcome

Timeframe: 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.

Total distance walked in 6 minutes in meters

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Six-Minute Walk Test Distance	71 meters Interval 49.0 to 94.0	27 meters Interval 3.0 to 50.0

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Comfortable Gait Speed	0.11 m/s Interval 0.06 to 0.15	0.02 m/s Interval -0.02 to 0.07

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Comfortable Gait Speed	0.14 m/s Interval 0.08 to 0.2	0.06 m/s Interval 0.0 to 0.12

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Comfortable Gait Speed	0.19 m/s Interval 0.13 to 0.25	0.06 m/s Interval 0.0 to 0.12

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Fast Gait Speed	0.22 m/s Interval 0.16 to 0.28	0.01 m/s Interval -0.05 to 0.07

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Fast Gait Speed	0.24 m/s Interval 0.17 to 0.32	0.09 m/s Interval 0.01 to 0.17

SECONDARY outcome

Timeframe: 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.

From 10-meter walk test, in meters per second

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Fast Gait Speed	0.28 m/s Interval 0.19 to 0.37	0.09 m/s Interval -0.01 to 0.18

SECONDARY outcome

Timeframe: 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.

Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Aerobic Fitness	1.3 mL/kg/min Interval 0.4 to 2.2	0.4 mL/kg/min Interval -0.5 to 1.3

SECONDARY outcome

Timeframe: 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.

Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Aerobic Fitness	2.0 mL/kg/min Interval 0.7 to 3.3	1.7 mL/kg/min Interval 0.3 to 3.1

SECONDARY outcome

Timeframe: 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.

Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Aerobic Fitness	1.9 mL/kg/min Interval 0.4 to 3.4	1.4 mL/kg/min Interval -0.2 to 3.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
PROMIS-Fatigue Scale	-1.7 T score Interval -4.0 to 0.6	0.0 T score Interval -2.3 to 2.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
PROMIS-Fatigue Scale	-3.0 T score Interval -5.5 to -0.5	1.0 T score Interval -1.6 to 3.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
PROMIS-Fatigue Scale	-1.1 T score Interval -3.7 to 1.5	-0.1 T score Interval -2.7 to 2.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Time to exhaustion during treadmill graded exercise test, recorded in minutes

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Exercise Capacity	1.8 minutes Interval 1.1 to 2.4	0.6 minutes Interval -0.1 to 1.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Time to exhaustion during treadmill graded exercise test, recorded in minutes

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Exercise Capacity	2.5 minutes Interval 1.5 to 3.4	1.6 minutes Interval 0.6 to 2.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Time to exhaustion during treadmill graded exercise test, recorded in minutes

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Exercise Capacity	3.3 minutes Interval 2.2 to 4.4	2.2 minutes Interval 1.1 to 3.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Peak Oxygen Consumption Rate	1.5 mL/kg/min Interval 0.5 to 2.5	0.2 mL/kg/min Interval -0.8 to 1.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Peak Oxygen Consumption Rate	2.1 mL/kg/min Interval 0.8 to 3.5	1.5 mL/kg/min Interval 0.0 to 2.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Peak Oxygen Consumption Rate	2.5 mL/kg/min Interval 0.8 to 4.2	1.5 mL/kg/min Interval -0.3 to 3.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Metabolic Cost of Gait	-0.08 mL/kg/m Interval -0.13 to -0.03	-0.05 mL/kg/m Interval -0.1 to 0.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Metabolic Cost of Gait	-0.10 mL/kg/m Interval -0.14 to -0.05	-0.08 mL/kg/m Interval -0.13 to -0.03

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Metabolic Cost of Gait	-0.12 mL/kg/m Interval -0.17 to -0.06	-0.11 mL/kg/m Interval -0.17 to -0.06

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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).

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
EuroQol 5D-5L (EQ-5D-5L)	-0.9 score Interval -1.8 to -0.1	-0.2 score Interval -1.1 to 0.7

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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).

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
EuroQol 5D-5L (EQ-5D-5L)	-0.6 score Interval -1.5 to 0.3	-0.4 score Interval -1.3 to 0.5

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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).

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
EuroQol 5D-5L (EQ-5D-5L)	-0.1 score Interval -1.0 to 0.8	-0.6 score Interval -1.5 to 0.3

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Activities-specific Balance Confidence Scale	-2.7 score Interval -7.2 to 1.7	-4.6 score Interval -9.1 to -0.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Activities-specific Balance Confidence Scale	1.6 score Interval -3.1 to 6.4	-1.8 score Interval -6.7 to 3.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

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.

Outcome measures

Measure	High-Intensity Interval Training n=27 Participants 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.	Moderate-Intensity Aerobic Training n=28 Participants 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.
Activities-specific Balance Confidence Scale	2.5 score Interval -2.7 to 7.7	0.6 score Interval -4.7 to 5.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Mean daily step count recorded with activity monitor, recorded as steps per day

Outcome measures

Measure	High-Intensity Interval Training n=25 Participants 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.	Moderate-Intensity Aerobic Training n=26 Participants 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.
Daily Walking Activity	-56 steps/day Interval -718.0 to 605.0	-102 steps/day Interval -816.0 to 612.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Mean daily step count recorded with activity monitor, recorded as steps per day

Outcome measures

Measure	High-Intensity Interval Training n=25 Participants 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.	Moderate-Intensity Aerobic Training n=26 Participants 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.
Daily Walking Activity	-299 steps/day Interval -1220.0 to 623.0	359 steps/day Interval -787.0 to 1505.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Mean daily step count recorded with activity monitor, recorded as steps per day

Outcome measures

Measure	High-Intensity Interval Training n=25 Participants 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.	Moderate-Intensity Aerobic Training n=26 Participants 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.
Daily Walking Activity	65 steps/day Interval -1381.0 to 1512.0	267 steps/day Interval -1529.0 to 2062.0

Adverse Events

High-Intensity Interval Training

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Moderate-Intensity Aerobic Training

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	High-Intensity Interval Training n=27 participants at risk 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.	Moderate-Intensity Aerobic Training n=28 participants at risk 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.
Nervous system disorders seizure	0.00% 0/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	3.6% 1/28 • Number of events 1 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
Musculoskeletal and connective tissue disorders fall with fracture	0.00% 0/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	3.6% 1/28 • Number of events 1 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
Nervous system disorders delirium	0.00% 0/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	3.6% 1/28 • Number of events 1 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
Nervous system disorders stroke	3.7% 1/27 • Number of events 1 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	0.00% 0/28 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study

Other adverse events

Measure	High-Intensity Interval Training n=27 participants at risk 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.	Moderate-Intensity Aerobic Training n=28 participants at risk 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.
Musculoskeletal and connective tissue disorders Pain/soreness	29.6% 8/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	25.0% 7/28 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
General disorders Fatigue	7.4% 2/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	7.1% 2/28 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
General disorders Lightheadedness	11.1% 3/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	14.3% 4/28 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study
General disorders Fall	11.1% 3/27 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study	0.00% 0/28 • Duration of participant enrollment post-randomization, which was approximately 4 months for participants who completed the study

Additional Information

Pierce Boyne

University of Cincinnati

Phone: 5135587499

Email: Pierce.Boyne@uc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place