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The goal of this clinical trial is to test ischemic conditioning (blood flow restriction) as a neuromodulatory technique to improve gait function in stroke. Neuromodulation is emerging as a promising adjunct strategy to facilitate changes in brain activity and improve motor behavior following a neurological injury such as stroke.
The main questions this trial aims to answer are:
Participants will take part in two sessions of ischemic conditioning where a cuff (similar to ones that measure blood pressure) will be placed around the thigh and inflated to one of two blood flow restriction pressures (real ischemic conditioning (real IC) and sham ischemic conditioning (sham IC)). Each participant will experience measures of brain activity and motor behavior testing before and after both sessions (real IC and sham IC).
Researchers will investigate ischemic conditioning as neuromodulation modality in stroke to see if ischemic conditioning can produce beneficial changes in brain activity and improvements on subsequent motor behavior tasks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ischemic Conditioning then Sham Ischemic Conditioning | Experimental | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience sham ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. |
|
| Sham Ischemic Conditioning then Ischemic Conditioning | Sham Comparator | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Real Ischemic Conditioning | Device | 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Corticomotor Excitability | Excitability of the primary lower limb motor cortex will be assessed using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the paretic leg. Higher values indicate more corticomotor excitability. | Changes in corticomotor excitability will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
| Change in Transcallosal Inhibition | Inhibition from the stimulated hemisphere to the non-stimulated hemisphere will be quantified as a measure of the ipsilateral silent period (iSP) using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the leg ipsilateral to TMS stimulation. Higher values indicate more inhibition from the stimulated hemisphere to the non-stimulated hemisphere. | Changes in transcallosal inhibition will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
| Change in Ankle Motor Control | Reaction time will be measured using a choice reaction time task involving rapid ankle dorsiflexion and plantarflexion movements in a custom built ankle-tracking device. Lower values reflect faster reaction times. Only dorsiflexion trials were analyzed to isolate TA activation, while both directions were included to minimize anticipatory activity. | Changes in ankle motor control will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
| Change in Lower Limb Strength | Participants will perform 3 trials each of maximum ankle dorsiflexion and plantarflexion strength. Higher values reflect more strength. | Changes in strength will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
| Measure | Description | Time Frame |
|---|---|---|
| Numerical Rating Scale (NRS) for Pain | Subjective measures of pain will be reported during ischemic conditioning and sham ischemic conditioning using a Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst pain). Ratings from each session will be averaged for each participant, and the final value will represent the mean pain rating across all participants for each experimental condition. | During each real and sham ischemic conditioning session. Ratings from each session will be averaged for each participant, and the final value will represent the mean pain rating across all participants for each experimental condition. |
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Inclusion Criteria:
Exclusion Criteria:
TMS General Exclusion Criteria:
IC General Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sangeetha Madhavan, PT, PhD | University of Illinois at Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Illinois Chicago | Chicago | Illinois | 60612 | United States |
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22 individuals with stroke were screened for eligibility. Of these, 2 were excluded prior to study procedures due to contraindications to IC. Of the 20 eligible participants, 1 withdrew for health reasons unrelated to study procedures (GI tract discomfort). Thus, 19 participants completed the study and experienced one session of IC and one session of sham-IC. All eligibility assessments and consent were conducted in person before randomization/ IC and sham-IC.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ischemic Conditioning Then Sham Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience sham ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Real Ischemic Conditioning: 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
| FG001 | Sham Ischemic Conditioning Then Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Real Ischemic Conditioning: 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ischemic Conditioning Then Sham Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience sham ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Real Ischemic Conditioning: 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Corticomotor Excitability | Excitability of the primary lower limb motor cortex will be assessed using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the paretic leg. Higher values indicate more corticomotor excitability. | All participants (n=19) who completed one session of real IC and one session of sham IC were analyzed. Participants (n=1) who withdrew from the study or did not complete the interventions were not included in the analyses. | Posted | Mean | Standard Deviation | millivolt (mV) | Changes in corticomotor excitability will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
|
Per participant: 1 week between interventions (real IC and sham IC), totaling 2 weeks.
Adverse events were monitored during each real IC and sham IC session using a structured questionnaire. Participants rated local and systemic symptoms (e.g., tingling, numbness) on a 0-4 scale. Definitions of adverse and serious adverse events aligned with ClinicalTrials.gov guidelines.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Real Ischemic Conditioning: 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tingling | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| PRS Training Lead | University of Illinois Chicago | (312) 996-4995 | awards@uic.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 4, 2025 | Jan 12, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Participants will be masked to the type of ischemic conditioning they receive (real or sham). Treatment arms/ session order (ischemic conditioning and sham ischemic conditioning) will be randomized.
| Sham Ischemic Conditioning | Device | Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
|
| BG001 | Sham Ischemic Conditioning Then Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. After a washout period of at least 1 week, participants will then experience ischemic conditioning. While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Real Ischemic Conditioning: 10-minute cycles of blood flow restriction (5 minutes) followed by blood flow release (5 minutes), repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Limb occlusion pressure | Mean | Standard Deviation | mmHg |
|
| Mini-Mental State Examination (MMSE) | The Mini-Mental State Examination (MMSE) score range is 0 to 30, with higher scores indicating better cognitive function, and a score of 24 or above generally considered normal, while lower scores suggest cognitive impairment, often categorized as mild (19-23), moderate (10-18), or severe (0-9). | Mean | Standard Deviation | units on a scale |
|
| Paretic FMLE | The Fugl-Meyer Lower Extremity (FMA-LE) assessment scale ranges from 0 to 34 points, with higher scores indicating better motor function, where 0 means no active motion and 2 signifies normal, complete performance for individual items, totaling 34 points for the subscale. This assessment evaluates hip, knee, ankle, and foot movements, including synergy patterns, with items rated on a 3-point scale (0, 1, 2) for a maximum of 34 points. | Mean | Standard Deviation | units on a scale |
|
| Ankle range of motion | Mean | Standard Deviation | degrees |
|
| Modified Rankin Scale | The Modified Rankin Scale (mRS) range is from 0 to 5, a 5-point scale assessing disability after neurological events like stroke, with 0 indicating no symptoms and 5 meaning the patient has died, while scores 1 through 4 represent increasing levels of disability, from slight to severe, with higher scores signifying greater dependency | Mean | Standard Deviation | units on a scale |
|
| Gait Speed | Mean | Standard Deviation | m/s |
|
| Endurance | Mean | Standard Deviation | m |
|
| OG001 | Sham Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. |
|
|
| Primary | Change in Transcallosal Inhibition | Inhibition from the stimulated hemisphere to the non-stimulated hemisphere will be quantified as a measure of the ipsilateral silent period (iSP) using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the leg ipsilateral to TMS stimulation. Higher values indicate more inhibition from the stimulated hemisphere to the non-stimulated hemisphere. | All participants (n=19) who completed one session of real IC and one session of sham IC were analyzed. Participants (n=1) who withdrew from the study or did not complete the interventions were not included in the analyses. | Posted | Mean | Standard Deviation | ms | Changes in transcallosal inhibition will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
|
|
|
| Primary | Change in Ankle Motor Control | Reaction time will be measured using a choice reaction time task involving rapid ankle dorsiflexion and plantarflexion movements in a custom built ankle-tracking device. Lower values reflect faster reaction times. Only dorsiflexion trials were analyzed to isolate TA activation, while both directions were included to minimize anticipatory activity. | All participants (n=19) who completed one session of real IC and one session of sham IC were analyzed. Participants (n=1) who withdrew from the study or did not complete the interventions were not included in the analyses. | Posted | Mean | Standard Deviation | ms | Changes in ankle motor control will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
|
|
|
| Primary | Change in Lower Limb Strength | Participants will perform 3 trials each of maximum ankle dorsiflexion and plantarflexion strength. Higher values reflect more strength. | All participants (n=19) who completed one session of real IC and one session of sham IC were analyzed. Participants (n=1) who withdrew from the study or did not complete the interventions were not included in the analyses. | Posted | Mean | Standard Deviation | pound-force (lbf) | Changes in strength will be calculated within and between sessions at baseline (Pre), immediate-post (Post), and 30-minutes-post (Post-30) one session of sham IC and real IC. |
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| Secondary | Numerical Rating Scale (NRS) for Pain | Subjective measures of pain will be reported during ischemic conditioning and sham ischemic conditioning using a Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst pain). Ratings from each session will be averaged for each participant, and the final value will represent the mean pain rating across all participants for each experimental condition. | All participants (n=19) who completed one session of real IC and one session of sham IC were analyzed. Participants (n=1) who withdrew from the study or did not complete the interventions were not included in the analyses. | Posted | Mean | Full Range | score on a scale | During each real and sham ischemic conditioning session. Ratings from each session will be averaged for each participant, and the final value will represent the mean pain rating across all participants for each experimental condition. |
|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 8 |
| 19 |
| EG001 | Sham Ischemic Conditioning | While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed around the paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Sham Ischemic Conditioning: Sham ischemic conditioning will mirror ischemic conditioning procedures, differing solely in cuff pressure during blood flow restriction to replicate to replicate perceived tightness without arterial blood flow restriction. | 0 | 19 | 0 | 19 | 0 | 19 |
| Numbness | Nervous system disorders | Systematic Assessment |
|
| Skin Irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Discomfort | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| Plantarflexion Post |
|
| Plantarflexion Post-30 |
|