Neuroplastic Changes Due to an Exercise Intervention That Aid in Lower Limb Recovery After Subcortical Stroke

This study aims to develop imaging-based biomarkers to assess which chronic stroke participant with lower extremity disability may respond or resist high intensity interval training (HIIT).

Previous research suggests that physical exercise training is safe and could help improve the walking speed of non-ambulatory stroke survivors. However, inter-individual variability in response to exercise is extraordinarily high regardless of adherence, and predictors of response remain elusive.

Chronic stroke survivors with lower limb disability resulting in slow walking speeds will participate in 12 weeks of cycling exercise at Emory University under the guidance of a physical exercise instructor, 3 days a week, for 25-60 minutes. During some of the exercise sessions, the investigators will collect blood lactate with a finger prick. Brain scans with an MRI before and after the 12 weeks of exercise will be done; motor function tests that include walking, sitting down, standing up, and turning around will be collected. Participants' memory and thinking will be assessed, and participants will fill out questionnaires about their health before and after their stroke, and well as questions about their diet.

The participation will last between 14-16 weeks (up to 42 study visits).

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Subcortical Lesions
• Intervention / Treatment: Behavioral: HIIT intervention

Detailed Description

This study will enroll 55 participants with chronic subcortical stroke in the 12-week HIIT intervention. Each chronic subcortical stroke participant will be asked to participate in the overall study protocol with pre-, during-, and post-intervention measurements. The HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at Emory University, administered by a trained exercise physiologist, for a total of 36 HIIT sessions. To accommodate stroke participants with lower limb disability, the study team will use a wheelchair accessible whole body trainer that uses a cycling motion. Each exercise session will start with a 5 minute warm up, followed by 20 minutes or more of moderate to intense cycling. Each session, the time will increase by one minute. The trained exercise physiologist may ask the participant to cruise (cycle at a comfortable pace), sprint (cycle faster), or climb (increase gear) in order to generate intervals of moderate and high intensity exercise during the session. The goal is to work the participant in a heart rate reserve (HRR) of 60-90%. The heart rate will constantly be monitored during the session. During HIIT sessions 1, 4, 7, 10, and 28 the participant's blood lactate will be measured via finger prick 7 times each session (for a total of 35 finger pricks) to assess if their lactate threshold is surpassed during HIIT. One week before the intervention and one week after, the participant will be asked to take part in an assessment of lower extremity motor function including walking speed, and a 90-minute MRI session for a brain scan. The overall goal of this study is to determine if the investigators can identify neurophysiological and imaging-derived biomarkers to predict whether a chronic subcortical stroke patient with lower extremity disability will respond to a 12-week HIIT intervention. Supported by preliminary data, the study team will build a model to consider the combined effects of blood lactate, baseline GABA, baseline CBF, baseline leg weakness, pre-stroke fitness, baseline VO2-max, age, sex, and comorbidities to predict improvements in walking speed after 12 weeks of HIIT.

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

Contacts and Locations

• Study Contact: Name: Susan Murphy; Phone Number: 404-712-1928; Email: smurph7@emory.edu
• Study Contact Backup: Name: Lisa Krishnamurthy, PhD; Phone Number: 404-712-5332; Email: lkrish2@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
      • Contact: Susan Murphy; Phone Number: 404-712-1928; Email: smurph7@emory.edu
    • Atlanta, Georgia, United States, 30322
      • Emory Rehabilitation Hospital
      • Contact: Susan Murphy; Phone Number: 404-712-1928; Email: smurph7@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• chronic left or right subcortical stroke as defined by 6 months or more after a cardiovascular accident
• lower extremity motor impairment due to stroke that causes a walking speed of less than 0.6 m/s during a 10m walk,
• age 18-80 years old, and
• Screen pass of the Stress test or Physician sign-off from the participant's health care team that they are cleared for a 12 week exercise intervention

Exclusion Criteria:

• MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia
• any neurodegenerative condition other than stroke that may lead to lower extremity impairment
• visual or auditory impairment that may hinder study procedures, and
• any medical condition that would preclude from participation in a physical exercise intervention program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HIIT intervention in chronic subcortical stroke participants; The HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at Emory University, administered by a trained exercise physiologist, for a total of 36 HIIT sessions.

Behavioral: HIIT intervention; Three weekly 25-60 minute cycling sessions for 12 weeks for a total of 36 HIIT sessions. Each exercise session will start with a 5 minute warm up, followed by 20 minutes or more of moderate to intense cycling. Each session, the time will increase by one minute. The trained exercise physiologist may ask the participant to cruise (cycle at a comfortable pace), sprint (cycle faster), or climb (increase gear) in order to generate intervals of moderate and high intensity exercise during the session. During HIIT sessions 1, 4, 7, 10, and 28 the participant's blood lactate will be measured via finger prick 7 times each session (for a total of 35 finger pricks) to assess if their lactate threshold is surpassed during HIIT. One week before the intervention and one week after, the participant will be asked to take part in an assessment of lower extremity motor function including walking speed, and a 90-minute MRI session for a brain scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Walking Speed Assessed by the 10-Meter Walk Test (10MWT)	Walking speed will be measured using the 10-Meter Walk Test (10MWT). Participants will be instructed to walk a measured 10-meter distance at their comfortable walking speed. The time required to traverse the designated distance will be recorded using a stopwatch, and walking speed will be calculated as distance divided by time and expressed in meters per second (m/s). Higher values indicate faster walking speed and improved ambulatory function.	12 weeks post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Mobility Assessed by the Timed Up and Go Test (TUG)	Functional mobility will be measured using the Timed Up and Go (TUG) test. Participants will be instructed to rise from a standard chair, walk 3 meters at a safe and comfortable pace, turn around, walk back to the chair, and sit down. The time required to complete the task will be recorded using a stopwatch and expressed in seconds (s). Lower completion times indicate better functional mobility and dynamic balance.	12 weeks post-intervention
Walking Endurance Assessed by the 6-Minute Walk Test (6MWT)	Walking endurance will be measured using the 6-Minute Walk Test (6MWT). Participants will be instructed to walk as far as possible along a designated walkway for 6 minutes at a self-selected pace, with rest periods permitted as needed according to standardized testing procedures. The total distance walked during the 6-minute period will be recorded and expressed in meters (m). Greater distances indicate better walking endurance and functional exercise capacity.	12 weeks post-intervention
Change in Resting-State Functional Connectivity of the Cognitive-Motor Network Assessed by MRI	Brain function will be assessed using resting-state functional magnetic resonance imaging (rsfMRI) acquired before and after the 12-week high-intensity interval training (HIIT) intervention. Functional connectivity will be quantified using echo-planar time-resolved imaging (EPTI) and expressed as z-transformed correlation values.	Baseline, 12 weeks post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Lactate Levels	Blood lactate levels in Millimoles per liter (mmol/L) will be measured at baseline and post-intervention.	Baseline, 12 weeks post-intervention

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Lisa Krishnamurthy, PhD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 17, 2026
• First Posted (Actual): June 23, 2026

Study Record Updates

• Last Update Posted (Actual): June 23, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: High intensity interval training
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 2025P010166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Raw images and interstitial processed images (including lesion masks), as well as demographic and motor testing data.
• IPD Sharing Time Frame: The data will become available 6 months after the last participant's data is collected
• IPD Sharing Access Criteria: Data will be made available to investigators at research institutions, for secondary analyses, upon written request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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