Ischemic Conditioning Improves Walking Function Post Stroke

Study Overview
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Brief Summary
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This innovative study will address scientific and clinical areas relatively unexplored in chronic stroke that could lead to greater recovery of walking. Ischemic Conditioning (IC) is a non-invasive, simple procedure that improves motor function, exercise performance and cardiovascular function in healthy controls, but it has never been applied to the stroke population. We postulate that IC enhances the recruitment of motoneurons and results in positive neural adaptations, improves vascular endothelial function and peripheral blood flow, and together these improvements result in an increased capacity to exercise and faster walking speed. Future studies will examine the effects of IC and traditional therapy at different time points of recovery post stroke, durability of IC, molecular mechanisms of neural and cardiovascular adaptation and the efficacy compared with other adjuncts.

Detailed Description
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This study will quantify the effects of Ischemic Conditioning and treadmill training on improvements in: walking speed, leg strength, neuromuscular fatigability and the hyperemic blood flow response to muscle contractions, and vascular endothelial function and aerobic exercise capacity. A randomized control design will be used with three groups of chronic stroke survivors enrolled for four weeks of training (3x/week; 12 sessions total). The groups are: IC + Treadmill Training, IC Sham + Treadmill Training, and IC only. We will also enroll a group of age- and sex-matched healthy control subjects who will undergo IC + Treadmill Training. All Aims will be tested concurrently over a five-year period. All studies will be performed in Cramer Hall at Marquette University in the Integrated Neural Engineering Rehabilitation Laboratories, the Human Performance Assessment Core, and the Physical Therapy Clinic. Randomization of stroke patients to the three intervention groups will be performed by using randomized block designs (randomly chosen block sizes of 3, 6 and 9). This number accounts for possible dropouts and the use of non- parametric methods.

Official Title
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Ischemic Conditioning Improves Walking Function Post Stroke

Conditions
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Stroke, Stroke, Ischemic, Stroke Hemorrhagic, Stroke, Cardiovascular

Intervention / Treatment
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* Procedure: Ischemic Conditioning
* Procedure: Ischemic Conditioning Sham
* Procedure: Treadmill Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Stroke Survivors): be ≥ 1 year post diagnosis of a unilateral, cortical stroke and have residual lower extremity paresis be between the ages of 18-85 be able to give informed consent walk slower than normative values based on age and sex Exclusion Criteria (Stroke Survivors): history of deep vein thrombosis or any condition in which transient ischemia to the lower extremity is contraindicated inability to follow 2 step commands chronic low back or hip pain history of substance abuse history of head trauma comorbid neurological disorder any uncontrolled medical condition pacemaker any condition where fatiguing contractions or resisted leg contractions are contraindicated inability to walk for 5 minute bouts on a treadmill with a harness supporting up to 50% of the body weight at 80% of over-ground self-selected walking speed. Inclusion Criteria (Healthy Control Subjects): be between ages of 18-85 be able to give informed consent Exclusion Criteria (Healthy Control Subjects): Those listed above for stroke survivors History of Stroke

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ischemic Conditioning + Treadmill Training<br>Study participants with prior history of stroke will receive both ischemic conditioning and treadmill training. | Procedure: Ischemic Conditioning<br>* Ischemic conditioning is a well-defined, non-invasive procedure which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 225 mmHg to occlude blood flow to the limb for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. In our study, participants assigned to the IC Only and IC + Treadmill Training groups will undergo twelve sessions of ischemic conditioning over a four-week period.<br>Procedure: Treadmill Training<br>* Participants will perform 3 treadmill training sessions/week for a 4 week period (12 sessions total). Treadmill training will immediately follow IC or IC Sham. Personnel performing the treadmill training will be blinded to the IC treatment group. Subjects will walk on a treadmill for six, 5-minute intervals. Walking speed will be continuously adjusted to maintain heart rate between 50% and 60% of age-adjusted heart rate reserve to minimize the confounder of intensity. If individuals cannot walk at 80% of their overground self-selected walking speed, for 5 minutes, they will be assisted into a body weight support harness. Body weight support will be adjusted (up to 50%) such that individuals can walk at 80% of their over ground walking speed for five minutes and adjusted accordingly throughout the session. Participants assigned to the Treadmill + IC and Treadmill + IC Sham groups will receive Treadmill Training.<br>|
| Placebo Comparator: Ischemic Conditioning Sham + Treadmill Training<br>Study participants with prior history of stroke will receive both ischemic conditioning sham and treadmill training. | Procedure: Ischemic Conditioning Sham<br>* Ischemic conditioning sham consists of the same setup as ischemic conditioning, which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 10 mmHg for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. 10 mmHg is a sufficient inflation pressure for study participants to perceive some cuff tightness, but is not high enough to occlude blood flow. In our study, participants assigned to the IC Sham + Treadmill Training groups will undergo twelve sessions of ischemic conditioning sham over a four-week period.<br>Procedure: Treadmill Training<br>* Participants will perform 3 treadmill training sessions/week for a 4 week period (12 sessions total). Treadmill training will immediately follow IC or IC Sham. Personnel performing the treadmill training will be blinded to the IC treatment group. Subjects will walk on a treadmill for six, 5-minute intervals. Walking speed will be continuously adjusted to maintain heart rate between 50% and 60% of age-adjusted heart rate reserve to minimize the confounder of intensity. If individuals cannot walk at 80% of their overground self-selected walking speed, for 5 minutes, they will be assisted into a body weight support harness. Body weight support will be adjusted (up to 50%) such that individuals can walk at 80% of their over ground walking speed for five minutes and adjusted accordingly throughout the session. Participants assigned to the Treadmill + IC and Treadmill + IC Sham groups will receive Treadmill Training.<br>|
| Active Comparator: Ischemic Conditioning Only<br>Study participants with prior history of stroke will receive only ischemic conditioning. | Procedure: Ischemic Conditioning<br>* Ischemic conditioning is a well-defined, non-invasive procedure which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 225 mmHg to occlude blood flow to the limb for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. In our study, participants assigned to the IC Only and IC + Treadmill Training groups will undergo twelve sessions of ischemic conditioning over a four-week period.<br>|
| Active Comparator: Healthy Control - Ischemic Conditioning + Treadmill Training<br>Healthy control participants will receive both ischemic conditioning and treadmill training. | Procedure: Ischemic Conditioning<br>* Ischemic conditioning is a well-defined, non-invasive procedure which consists of inflating a blood pressure cuff around a limb (in our study, the paretic leg), inflating the cuff to 225 mmHg to occlude blood flow to the limb for 5 minutes, releasing the cuff for 5 minutes, and repeating 5 times. In our study, participants assigned to the IC Only and IC + Treadmill Training groups will undergo twelve sessions of ischemic conditioning over a four-week period.<br>Procedure: Treadmill Training<br>* Participants will perform 3 treadmill training sessions/week for a 4 week period (12 sessions total). Treadmill training will immediately follow IC or IC Sham. Personnel performing the treadmill training will be blinded to the IC treatment group. Subjects will walk on a treadmill for six, 5-minute intervals. Walking speed will be continuously adjusted to maintain heart rate between 50% and 60% of age-adjusted heart rate reserve to minimize the confounder of intensity. If individuals cannot walk at 80% of their overground self-selected walking speed, for 5 minutes, they will be assisted into a body weight support harness. Body weight support will be adjusted (up to 50%) such that individuals can walk at 80% of their over ground walking speed for five minutes and adjusted accordingly throughout the session. Participants assigned to the Treadmill + IC and Treadmill + IC Sham groups will receive Treadmill Training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self Selected Walking Speed | We will measure how fast participants walk during the 10 meter walk test. | Change from baseline to 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee Extensor Leg Strength | Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention | Change from baseline to 4 weeks. | 
| Knee Extensor Fatigability | Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention | Change from baseline to 4 weeks. | 
| Flow Mediated Dilation of Non-Paretic Brachial Artery and Paretic Popliteal Artery | Pre-treatment and after 1, 6, and 12 sessions of ischemic conditioning. We will also test 1 month post intervention | Change from baseline to 4 weeks. | 
| Peak Oxygen Consumption | Using a recumbent bicycle and metabolic cart, we will test whole body oxygen consumption during a graded exercise test | Change from baseline to 4 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Rehabilitation, Ischemic Conditioning, Treadmill Training