[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06059872":3,"trial-entities:NCT06059872":110,"trial-summary:NCT06059872":113},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":23,"study_type":28,"primary_purpose":29,"phases":30,"enrollment_info":32,"interventions":35,"primary_outcomes":42,"secondary_outcomes":53,"sex":67,"minimum_age":68,"maximum_age":69,"healthy_volunteers":15,"eligibility_criteria":70,"std_ages":81,"locations":84,"central_contacts":103,"overall_officials":106,"references":108,"see_also_links":109},"NCT06059872","N4537-R","Biomarkers of Reaction To HIIT Exercise","What Makes a Responder, a Responder? Biomarkers to Help Identify Responders and Resistors to High-intensity Interval Training for Lower Extremity Chronic Stroke","RECRUITING","2027-12-01","2026-03","2026-03-27","2024-01-01","VA Office of Research and Development","FED",false,"Stroke survivors with lower limb disability can improve their walking speed with high-intensity interval training (HIIT) rehabilitation therapy. However, some individuals may not respond to HIIT even when fully adherent to the program. To address this, the investigators propose to build a predictive model that identifies if a Veteran with chronic subcortical stroke will improve their walking speed with HIIT by incorporating blood lactate as an early predictor of exercise response, and inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and regional cerebral blood flow (CBF) as predictors of the brain's potential to respond, while also taking into consideration other factors such as comorbidities, demographics, and fitness levels.","Most chronic subcortical stroke survivors have difficulty walking, but few predictors can help identify if a patient will respond to an exercise regimen and improve their function. To enhance precision rehabilitation for chronic subcortical stroke patients, personalized aerobic exercise interventions are crucial. This requires the development of innovative technologies that can identify the essential neurobiological factors to predict intervention response and enable clinicians to determine individualized rehabilitation targets. Lactate is one exciting new target that acts as a molecular messenger between the periphery and the brain. For lactate to have an impact on other organs, including the brain, there must be a substantial increase in its level in the bloodstream from baseline. When the blood lactate threshold is surpassed during exercise, lactate acts on the brain metabolically via the TCA cycle. Embedded within the TCA cycle is the means to increase or decrease neurotransmitter concentrations such as GABA and glutamate. Gamma-aminobutyric acid (GABA), the brain's major inhibitory neurotransmitter, is a new treatment target that promotes neural plasticity during stroke rehabilitation. Drawing from the framework of personalized rehabilitation approaches and our preliminary data, the investigators propose to build a predictive model that can identify if a chronic subcortical stroke patient will respond to exercise training. This model aims to predict improvements in walking speed by incorporating blood lactate as an early predictor of exercise response and GABA and cerebral blood flow (CBF) as predictors of the brain's potential to respond, in addition to other influencing factors such as comorbidities, demographics, and fitness levels. The overarching hypothesis is that robust neurophysiological factors driven by lactate can differentiate responders from resistors and that these factors can be applied clinically as biomarkers to predict functional outcomes after a 12-week HIIT intervention. The investigators will assess improvements in walking speed in 48 Veterans with lower limb disability due to chronic subcortical stroke in response to a 36-session (12-week) HIIT intervention. After the intervention, each adherent participant who improves their walking speed to greater than 0.6 m\u002Fs will be categorized as a responder while each adherent participant who does not improve their walking speed will be categorized as a resistor. At baseline and after 12 weeks of HIIT the investigators will evaluate walking speed, balance, leg strength, and endurance to identify resistors and responders to HIIT and collect a) GABA from the primary sensory-motor leg area using single-voxel magnetic resonance spectroscopy, b) CBF from the whole brain using pseudo-Continuous Arterial Spin Labeling MRI and c) VO2 max to evaluate change in CRF. During the intervention, the investigators will collect blood lactate via finger prick during sessions 1, 4, 7, 10, and 28 to assess its potential as an early predictor of exercise response. In aim 1 the investigators determine if surpassing the lactate threshold during the first 4 weeks of HIIT predicts the change in walking speed to 0.6 m\u002Fs, from pre- to post-HIIT. If lactate proves to be a robust early marker of functional response to exercise, the investigators will have an easy-to-deploy predictor of who will best benefit from HIIT. In aim 2 the investigators will determine if (a) baseline GABA and\u002For CBF predict improvements in walking speed from baseline to after HIIT and (b) if a change in GABA and\u002For CBF relate to a change in walking speed. The investigators aim to establish neurophysiological correlates of improving function with HIIT to better understand the mechanisms. Finally, in aim 3 the investigators will a predictive machine learning algorithm of who will improve their walking speed with HIIT using factors of blood lactate, baseline GABA and CBF, baseline leg weakness and VO2-max, pre-stroke fitness, age, sex, and comorbidities. The overarching objective is to develop a model to predict which Veteran with chronic stroke will respond to a 12-week exercise program.",[19,20,21,22],"Stroke","Stroke Rehabilitation","Lower Extremity Weakness, Spastic","Walking, Difficulty",[24,25,26,27],"Predictors of Stroke Rehabilitation","Biomarkers of Stroke Rehabilitation","Exercise Intervention","Neuroimaging","INTERVENTIONAL","TREATMENT",[31],"NA",{"count":33,"type":34},55,"ESTIMATED",[36],{"type":37,"name":38,"description":39,"armGroupLabels":40},"OTHER","High Intensity Interval Training (HIIT)","HIIT consists of three weekly 25-60 minute cycling sessions for 12 weeks at the Atlanta VA, administered by a trained exercise physiologist, for a total of 36 HIIT sessions.",[41],"Chronic Stroke with lower limb disability",[43,47,50],{"measure":44,"description":45,"timeFrame":46},"10 m walk test on a GAITRite mat","To assess short-distance walking speed and gait characteristics.","baseline (week 1) and after the completion of 12 weeks of exercise (week 14)",{"measure":48,"description":49,"timeFrame":46},"Timed-Up-and-Go (TUG) test","To assess short-distance walking and postural control.",{"measure":51,"description":52,"timeFrame":46},"6-minute walk test","To assess endurance.",[54,58,61,64],{"measure":55,"description":56,"timeFrame":57},"Blood lactate change during HIIT session","To assess if the participant increases their blood lactate during the HIIT session.","On exercise day 1, 4, 7, 10, and 28. The total number of exercise days is 36 (3 times per week for 12 weeks).",{"measure":59,"description":60,"timeFrame":46},"MEGA-PRESS Magnetic Resonance Spectroscopy","To assess GABA from the ipsilesional and contralesional leg areas of the brain.",{"measure":62,"description":63,"timeFrame":46},"pseudo Continuous Arterial Spin Labeling MRI","To assess whole brain regional cerebral blood flow.",{"measure":65,"description":66,"timeFrame":46},"Graded treadmill or bike testing","To estimate VO2-max.","ALL","18 Years","89 Years",{"inclusion":71,"exclusion":75,"raw_text":80},[72,73,74],"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\u002Fs during a 10m walk","Veteran status",[76,77,78,79],"MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia","any neurodegenerative condition other than stroke that may lead to lower extremity impairment","a visual or auditory impairment that may hinder study procedures","any medical condition that would preclude participation in a physical exercise intervention program","Inclusion Criteria:\n\n* chronic left or right subcortical stroke as defined by 6 months or more after a cardiovascular accident\n* lower extremity motor impairment due to stroke that causes a walking speed of less than 0.6 m\u002Fs during a 10m walk\n* Veteran status\n\nExclusion Criteria:\n\n* MRI contraindications, including implanted cardiac pacemakers and severe claustrophobia\n* any neurodegenerative condition other than stroke that may lead to lower extremity impairment\n* a visual or auditory impairment that may hinder study procedures\n* any medical condition that would preclude participation in a physical exercise intervention program",[82,83],"ADULT","OLDER_ADULT",[85],{"facility":86,"status":8,"city":87,"state":88,"zip":89,"country":90,"contacts":91,"geoPoint":100},"Atlanta VA Medical and Rehab Center, Decatur, GA","Decatur","Georgia","30033-4004","United States",[92,98],{"name":93,"role":94,"phone":95,"phoneExt":96,"email":97},"Lisa C Krishnamurthy, PhD","CONTACT","404-321-6111","6235","Lisa.Krishnamurthy@va.gov",{"name":93,"role":99},"PRINCIPAL_INVESTIGATOR",{"lat":101,"lon":102},33.77483,-84.29631,[104],{"name":93,"role":94,"phone":105,"phoneExt":96,"email":97},"(404) 321-6111",[107],{"name":93,"affiliation":86,"role":99},[],[],{"nct_id":4,"conditions":111,"biomarkers":112},[19],[],{"nct_id":4,"found":114,"summary":115,"prompt_version":125},true,{"design":116,"status":117,"heading":118,"summary":119,"follow_up":120,"word_count":121,"commitments":122,"compensation":123,"drugs_mentioned":124},"This is an interventional study planning to enroll 55 participants. It is not specified if it is randomized or blinded.","completed","Biomarkers of Reaction To HIIT Exercise for Stroke Survivors","This study is looking at how High-Intensity Interval Training (HIIT) affects walking ability in stroke survivors. HIIT involves three weekly cycling sessions for 12 weeks. Researchers want to understand why some people respond well to HIIT and others don't. They will look at factors like blood lactate (a chemical in your blood after exercise) and brain chemicals (like GABA) to predict who will improve their walking speed. This study is for Veterans aged 18 to 89 who had a stroke at least six months ago and have difficulty walking. Success in this study means seeing improvements in walking tests like the 10-meter walk, Timed-Up-and-Go, and 6-minute walk tests after 12 weeks of exercise. The current status of this study is unclear.","Your walking ability will be assessed at baseline (week 1) and after 12 weeks of exercise (week 14).",121,"You would participate in three weekly 25-60 minute cycling sessions for 12 weeks, for a total of 36 sessions. Your walking ability will be tested at the beginning and after 12 weeks of exercise.","Not stated in the trial record.",[],"v2"]