Ischemic Conditioning for Stroke

(PLM Trial)

Overseen By Alicen Whitaker-Hilbig, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Blood clots, Severe COVID-19, 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: Unknown

Duration: 1 day per session

55 Participants Needed

Trial Summary

What is the purpose of this trial?

Stroke survivors have compromised vascular function which may contribute to secondary stroke risk, cardiovascular disease, and may limit their exercise tolerance. No studies have examined how femoral blood flow responds to both passive leg movement, a measure of microvascular function, as well as active leg contractions, a measure of the hyperemic response to exercise. Leg muscles with a reduced blood flow response to movement could be associated with decreased neuromuscular function, such as leg strength and fatigue. Preliminary data showing a single bout of ischemic conditioning may improve vascular function and muscle activation in healthy adults and individuals post-stroke. Therefore, the investigators want to examine if ischemic conditioning will also improve the blood flow response to passive leg movements as well as during single leg active contractions.

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 data supports the effectiveness of the treatment Ischemic Conditioning for Stroke?

Research suggests that remote ischemic conditioning (RIC) may help improve outcomes for stroke patients by protecting brain cells and reducing inflammation. Some studies show it could be beneficial when used soon after a stroke, and it might also help with recovery by supporting brain repair. ^{1 2 3 4 5}

How is remote ischemic conditioning different from other stroke treatments?

Remote ischemic conditioning (RIC) is unique because it involves temporarily restricting blood flow to a limb, like using a blood pressure cuff, to protect the brain during a stroke. This noninvasive method is different from standard treatments like clot-busting drugs or surgery, as it aims to enhance the body's natural protective responses without directly targeting the stroke site. ^{1 6 7 8 9}

Research Team

Matthew Durand, PhD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for stroke survivors aged 18-85 with residual hemiparesis from a stroke at least 6 months prior, and healthy adults aged 18-30. Participants must be able to understand instructions and communicate in English. Exclusions include severe mobility issues, recent severe COVID-19 or head trauma, other neurological disorders, heart attack within the last year, high blood pressure, pregnancy/breastfeeding, or conditions where leg compression is unsafe.

Inclusion Criteria

I had a stroke 6+ months ago, have some paralysis, can follow commands, and speak English.

Exclusion Criteria

Other significant medical condition likely to influence study or jeopardize safety as assessed by the Primary Investigator

I have not had a head injury or concussion in the last 6 months.

I have had a heart attack in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo ischemic conditioning with varying cuff pressures to assess effects on leg blood flow and muscle function

1 day per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in femoral blood flow and muscle function after ischemic conditioning

3 hours post-treatment

Post-Conditioning Assessment

Assessment of femoral blood flow response to neuromuscular fatigue task

15 minutes post-conditioning

Treatment Details

Interventions

• Ischemic Conditioning

Trial Overview The study investigates whether ischemic conditioning can improve blood flow response during passive and active leg movements in individuals post-stroke. It aims to see if this treatment could enhance vascular function and muscle activation which might be compromised after a stroke.

Participant Groups

Group I: Ischemic Conditioning - Low Experimental Treatment 1 Intervention

During each testing session, the investigators will be measuring how one treatment of ischemic conditioning effects leg blood flow and muscle function. One day participants will receive a low cuff inflation pressure on the leg, called ischemic conditioning - low (25 mmHg).

Group II: Ischemic Conditioning - High Experimental Treatment 1 Intervention

During each testing session, the investigators will be measuring how one treatment of ischemic conditioning effects leg blood flow and muscle function. One day participants will receive a high cuff inflation pressure on the leg, called ischemic conditioning - high (225 mmHg).

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Marquette University

Collaborator

Trials

68

Recruited

202,000+

Findings from Research

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]

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]

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]

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]

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]

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]

Remote ischemic conditioning (RIC) is a safe and easily implementable procedure that may reduce biomarkers of heart damage and infarct size in patients with acute myocardial infarction and ischemic stroke.

Despite its safety and potential benefits in reducing heart damage, the efficacy of RIC in improving clinical outcomes for ischemic stroke patients is still uncertain and requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences. Saccaro, LF., Aimo, A., Emdin, M., et al.[2021]

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]

References

1. United States 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. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning for Motor Recovery after Acute Ischemic Stroke. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Time from Onset to Remote Ischemic Conditioning and Clinical Outcome After Acute Moderate Ischemic Stroke. [2023]

4. United States 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A review of remote ischemic conditioning as a potential strategy for neural repair poststroke. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Remote ischemic conditioning for acute stroke patients treated with thrombectomy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta-analysis from randomized controlled trials. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning in Ischemic Stroke and Myocardial Infarction: Similarities and Differences. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Remote Limb Ischemic Conditioning during Cerebral Ischemia Reduces Infarct Size through Enhanced Collateral Circulation in Murine Focal Cerebral Ischemia. [2018]