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

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).

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Behavioral: Moderate-Intensity Aerobic Training; Behavioral: High-Intensity Interval Training

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Newark, Delaware, United States, 19713
      • University of Delaware
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Moderate-Intensity Aerobic Training	Behavioral: 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.
Experimental: High-Intensity Interval Training	Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six-Minute Walk Test Distance	Total distance walked in 6 minutes in meters	Change Six-Minute Walk Test Distance from Baseline to 4 Weeks
Six-Minute Walk Test Distance	Total distance walked in 6 minutes in meters	Change Six-Minute Walk Test Distance from Baseline to 8 Weeks
Six-Minute Walk Test Distance	Total distance walked in 6 minutes in meters	Change Six-Minute Walk Test Distance from Baseline to 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comfortable Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 4 Weeks
Comfortable Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 8 Weeks
Comfortable Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 12 Weeks
Fast Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 4 Weeks
Fast Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 8 Weeks
Fast Gait Speed	From 10-meter walk test, in meters per second	Change from Baseline to 12 Weeks
Aerobic Fitness	Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 4 Weeks
Aerobic Fitness	Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 8 Weeks
Aerobic Fitness	Oxygen consumption rate at ventilatory threshold during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 12 Weeks
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.	Change from Baseline to 4 Weeks
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.	Change from Baseline to 8 Weeks
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.	Change from Baseline to 12 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise Capacity	Time to exhaustion during treadmill graded exercise test, recorded in minutes	Change from Baseline to 4 Weeks
Exercise Capacity	Time to exhaustion during treadmill graded exercise test, recorded in minutes	Change from Baseline to 8 Weeks
Exercise Capacity	Time to exhaustion during treadmill graded exercise test, recorded in minutes	Change from Baseline to 12 Weeks
Peak Oxygen Consumption Rate	Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 4 Weeks
Peak Oxygen Consumption Rate	Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 8 Weeks
Peak Oxygen Consumption Rate	Peak oxygen consumption rate during treadmill graded exercise test, in milliliters per kilogram body mass per minute	Change from Baseline to 12 Weeks
Metabolic Cost of Gait	Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter	Change from Baseline to 4 Weeks
Metabolic Cost of Gait	Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter	Change from Baseline to 8 Weeks
Metabolic Cost of Gait	Oxygen consumption rate relative to speed during treadmill graded exercise test, in milliliters per kilogram body mass per meter	Change from Baseline to 12 Weeks
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).	Change from Baseline to 4 Weeks
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).	Change from Baseline to 8 Weeks
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).	Change from Baseline to 12 Weeks
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.	Change from Baseline to 4 Weeks
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.	Change from Baseline to 8 Weeks
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.	Change from Baseline to 12 Weeks
Daily Walking Activity	Mean daily step count recorded with activity monitor, recorded as steps per day	Change from Baseline to 4 Weeks
Daily Walking Activity	Mean daily step count recorded with activity monitor, recorded as steps per day	Change from Baseline to 8 Weeks
Daily Walking Activity	Mean daily step count recorded with activity monitor, recorded as steps per day	Change from Baseline to 12 Weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Kansas Medical Center; Children's Hospital Medical Center, Cincinnati; University of Delaware
• Investigators: Principal Investigator: Pierce Boyne, DPT, PhD, University of Cincinnati

Publications and helpful links

General Publications

• Miller A, Reisman DS, Billinger SA, Dunning K, Doren S, Ward J, Wright H, Wagner E, Carl D, Gerson M, Awosika O, Khoury J, Kissela B, Boyne P. Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial. Trials. 2021 Jul 16;22(1):457. doi: 10.1186/s13063-021-05419-x.
• Boyne P, Billinger SA, Reisman DS, Awosika OO, Buckley S, Burson J, Carl D, DeLange M, Doren S, Earnest M, Gerson M, Henry M, Horning A, Khoury JC, Kissela BM, Laughlin A, McCartney K, McQuaid T, Miller A, Moores A, Palmer JA, Sucharew H, Thompson ED, Wagner E, Ward J, Wasik EP, Whitaker AA, Wright H, Dunning K. Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial. JAMA Neurol. 2023 Apr 1;80(4):342-351. doi: 10.1001/jamaneurol.2023.0033.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2019
• Primary Completion (Actual): April 25, 2022
• Study Completion (Actual): April 25, 2022

Study Registration Dates

• First Submitted: November 26, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (Actual): November 30, 2018

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Rehabilitation; Locomotion; Intensity; Aerobic; Dosing
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 2017-5325; R01HD093694 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We deposited the final, de-identified dataset and data documentation into the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Data and Specimen Hub (DASH) archive (URL below)
• IPD Sharing Time Frame: Data are available now and should remain available indefinitely.
• IPD Sharing Access Criteria: Established by the repository
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 424597

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No