Ischemic Conditioning for Stroke Recovery

Recruiting at 1 trial location

Overseen By Jennifer Nguyen, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Blood clots, Neurological disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a treatment called ischemic conditioning to help stroke survivors with muscle fatigue. The study examines whether improving blood flow to leg muscles can reduce tiredness during activities like walking. Participants will either undergo the actual treatment or a similar sham (inactive) procedure for comparison. The trial seeks individuals who had a stroke at least six months ago and can speak English. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could enhance rehabilitation for stroke survivors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that ischemic conditioning is safe for stroke recovery?

Research has shown that ischemic conditioning, a non-invasive procedure, is generally well-tolerated by patients. Studies have found that individuals with conditions like sudden strokes and certain types of brain bleeds handle it well. Some may experience mild side effects such as arm pain, redness, or dizziness, but these are usually minor. Previous research did not find any serious side effects. Overall, ischemic conditioning appears to be a safe way to improve blood flow and reduce muscle fatigue. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Ischemic conditioning is unique because it uses a non-invasive approach to potentially aid stroke recovery. Unlike standard stroke treatments that often involve medication or surgical interventions, ischemic conditioning involves temporarily restricting blood flow to a limb using a blood pressure cuff, which may help the brain adapt and recover more effectively after a stroke. Researchers are excited about this technique because it could offer a simple, low-risk method to enhance recovery, potentially making it accessible to more patients. Additionally, its mechanism of action is different from existing treatments, as it focuses on conditioning the body to improve resilience and repair, rather than directly altering the brain or blood vessels.

What evidence suggests that ischemic conditioning is effective for stroke recovery?

Research has shown that ischemic conditioning, which participants in this trial may receive, can improve blood flow to muscles and potentially reduce muscle fatigue. Studies have found that this method greatly enhances recovery, particularly for stroke patients. Specifically, it improved brain recovery and decreased the size of damaged brain areas. Patients who received ischemic conditioning often had better recovery outcomes compared to those who did not. This technique involves temporarily stopping blood flow to a limb, and when restored, it is believed to protect and strengthen the affected muscles and nerves. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-85 who had a stroke at least 6 months ago and can consent to participate. It's not suitable for those with blood clot history, chronic pain that affects testing, recent heart attack, pregnancy, other neurological disorders or certain health conditions.

Inclusion Criteria

Able to give informed consent

It has been over 6 months since my stroke.

English speaking

Exclusion Criteria

Your blood pressure when you are resting is very high.

I have chronic pain that lasts a long time.

I cannot follow 2-step commands.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Aim 1 Testing

Participants undergo testing to measure functional sympatholysis response and muscle fatigue metrics

6 visits for stroke survivors, 3 visits for controls

6 visits (in-person) for stroke survivors, 3 visits (in-person) for controls

Aim 2 Testing

Examination of vasoactive effects of norepinephrine and acetylcholine in the cutaneous microvasculature

2 visits for stroke survivors, 1 visit for controls

2 visits (in-person) for stroke survivors, 1 visit (in-person) for controls

Aim 3 Intervention

Participants undergo ischemic conditioning or sham intervention to assess effects on functional sympatholysis and muscle fatigue

6 weeks

10 visits (in-person) over 6 weeks

Follow-up

Participants are monitored for changes in functional sympatholysis and muscle fatigue metrics post-intervention

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ischemic Conditioning

Trial Overview

The study tests ischemic conditioning—a non-invasive method thought to improve blood flow and reduce muscle fatigue in the leg of stroke survivors. Researchers want to see if this intervention helps people post-stroke perform tasks longer without getting tired.

How Is the Trial Designed?

Group I: Ischemic Conditioning Experimental Treatment 1 Intervention

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 will receive six sessions of ischemic conditioning over the course of two weeks.

Group II: Ischemic Conditioning Sham Placebo Group 1 Intervention

There will also be an IC Sham group which is identical to the IC intervention, except the cuff will only be inflated to 10 mmHg, which is not a high enough pressure to occlude arterial blood flow.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Remote ischemic conditioning (RIC) may enhance rehabilitation after ischemic stroke by triggering the body's own protective mechanisms, although its specific effects on the neural repair process are still not fully understood.

This review suggests that RIC could be a promising therapeutic strategy for stroke rehabilitation, highlighting the need for further research to clarify its mechanisms and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of remote ischemic conditioning as a potential strategy for neural repair poststroke. Yu, W., Ren, C., Ji, X.[2023]

Remote ischemic conditioning (RIC) was found to be safe and feasible for 20 patients with acute ischemic stroke undergoing endovascular treatment, with no serious RIC-related adverse events reported during the study.

At the 3-month follow-up, 55% of patients achieved functional independence, suggesting potential benefits of RIC, although further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischemic conditioning for acute stroke patients treated with thrombectomy. Zhao, W., Che, R., Li, S., et al.[2022]

In a study of 1,776 patients with acute moderate ischemic stroke, early initiation of Remote Ischemic Conditioning (RIC) within 24 hours of stroke onset was associated with an 8.1% higher likelihood of achieving excellent functional outcomes at 90 days compared to usual care.

No significant benefits were observed for patients who received RIC treatment later (24-48 hours after onset) compared to the control group, indicating that timing of RIC is crucial for its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time from Onset to Remote Ischemic Conditioning and Clinical Outcome After Acute Moderate Ischemic Stroke. Cui, Y., Chen, YN., Nguyen, TN., et al.[2023]

Remote ischemic conditioning (RIC) did not significantly improve functional outcomes in patients with acute stroke compared to sham treatment, as shown in a study of 1500 patients with a median follow-up of 90 days.

There were no significant differences in serious adverse events between the RIC and sham groups, although RIC was associated with a higher incidence of upper extremity pain and skin petechiae.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial. Blauenfeldt, RA., Hjort, N., Valentin, JB., et al.[2023]

Remote ischemic conditioning (RIC) combined with intravenous thrombolysis (IVT) is safe for treating acute ischemic stroke, showing no significant differences in hemorrhagic transformation or adverse events compared to a sham treatment in a study of 49 patients.

While RIC did not improve overall functional outcomes measured by the modified Rankin Scale or NIHSS scores, it significantly reduced levels of high-sensitivity C-reactive protein, suggesting potential anti-inflammatory benefits that merit further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke. He, YD., Guo, ZN., Qin, C., et al.[2021]

Remote ischemic conditioning (RIC) was well tolerated in a pilot study of 26 patients with acute ischemic stroke, with 49 out of 52 treatment cycles completed, suggesting it is a safe intervention.

Patients receiving RIC showed a significant improvement in neurological outcomes at day 90, with a lower NIHSS score compared to the sham group, indicating potential efficacy in enhancing recovery after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke. England, TJ., Hedstrom, A., O'Sullivan, S., et al.[2022]

A single application of remote ischemic conditioning (RIC) in 47 patients with chronic cerebral vascular stenosis showed significant changes in inflammatory and coagulation markers, particularly in those with cerebral arteriostenosis, indicating its potential neuroprotective effects.

In patients with cerebral arteriostenosis, RIC led to a decrease in fibrinogen levels and an increase in interleukin-6, suggesting a complex interplay of pro-inflammatory and anti-coagulation effects, while older age negatively impacted several biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Anti-Inflammatory and Anti-Coagulation Effects of One-Time Application of Remote Ischemic Conditioning in Patients With Subacute/Chronic Cerebral Arteriostenosis and Venostenosis. Song, SY., Jiao, BL., Lan, D., et al.[2023]

In a study involving 50 mice, the per-conditioning (per-RIC) method of remote ischemic conditioning was found to be the most effective in protecting the brain during focal cerebral ischemia, as it resulted in a significantly smaller infarct volume compared to other conditioning methods.

The per-RIC group also showed a greater increase in cerebral blood flow and larger collateral circulation, suggesting that enhancing collateral circulation may contribute to the protective effects observed with per-RIC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Limb Ischemic Conditioning during Cerebral Ischemia Reduces Infarct Size through Enhanced Collateral Circulation in Murine Focal Cerebral Ischemia. Kitagawa, K., Saitoh, M., Ishizuka, K., et al.[2018]

The SERIC-IVT trial is evaluating the effectiveness and safety of remote ischemic conditioning (RIC) combined with intravenous thrombolysis (IVT) in 558 patients with acute ischemic stroke, aiming to improve functional outcomes at 90 days.

The study will assess whether RIC can lead to a 13.14% increase in favorable outcomes, measured by the modified Rankin Scale, while also monitoring for safety issues such as mortality and adverse events within the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of remote ischemic conditioning combined with intravenous thrombolysis for acute ischemic stroke: A multicenter, randomized, parallel-controlled clinical trial (SERIC-IVT) Study design and protocol. Abuduxukuer, R., Guo, ZN., Zhang, P., et al.[2023]

Remote ischemic conditioning (RIC) has been shown to significantly reduce the recurrence of ischemic stroke and improve patient prognosis at 90 days, based on a meta-analysis of 6392 patients from 17 randomized controlled trials.

RIC is considered safe, as it does not increase the risk of serious adverse events like death or intracerebral hemorrhage, although it may cause some benign RIC-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta-analysis from randomized controlled trials. Kan, X., Yan, Z., Wang, F., et al.[2023]

In a study of 27 patients with hemiplegia from acute ischemic stroke, chronic remote ischemic conditioning (RIC) for 90 days significantly improved lower limb motor function compared to the control group, as indicated by higher Fugl-Meyer Assessment scores.

Chronic RIC also led to a significant increase in serum levels of epidermal growth factor (EGF), suggesting a potential mechanism for its beneficial effects on recovery, although overall functional outcomes did not show a significant difference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning for Motor Recovery after Acute Ischemic Stroke. Yu, W., Ren, C., Du, J., et al.[2023]

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