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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a technique called ischemic conditioning, which may improve blood flow and muscle function in stroke survivors. Researchers aim to determine if this technique can enhance blood flow in the legs during both passive movements and active exercises. The trial will test two different pressure levels to identify the more effective option. Individuals who had a stroke at least six months ago and experience residual weakness on one side might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance rehabilitation techniques 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 survivors?

Research has shown that ischemic conditioning is generally safe for patients. Studies have found that people who have had a stroke usually tolerate this treatment well. Common side effects are mild and may include arm pain, redness, or slight swelling where the treatment is applied. Some people also feel dizzy, but these effects are usually not serious.

In past research, ischemic conditioning did not cause any major health problems, suggesting it is safe for people, especially those who have had a stroke. The treatment aims to improve blood flow and muscle function, which could help stroke survivors.

Overall, evidence suggests that ischemic conditioning is a safe option for those considering joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ischemic conditioning for stroke because it offers a novel approach by using pressure cuffs to improve blood flow and muscle function in the legs. Unlike traditional stroke treatments that often involve medication or surgical interventions, this method focuses on non-invasive physical conditioning. The unique aspect here is the adjustable cuff pressure, with both high (225 mmHg) and low (25 mmHg) settings, which might provide tailored benefits based on individual needs. This technique could potentially enhance recovery by promoting better blood circulation and muscle performance without the need for drugs or surgery.

What evidence suggests that ischemic conditioning could be effective for improving blood flow and muscle function in stroke survivors?

Research has shown that a treatment called ischemic conditioning can aid recovery after a stroke. Studies have found that this treatment can enhance brain recovery and reduce brain damage from a stroke. It also correlates with better overall outcomes for stroke patients. In this trial, participants will receive either high or low cuff inflation pressure as part of the ischemic conditioning treatment. Early findings suggest that ischemic conditioning might improve blood flow and muscle function, particularly in the legs. This could alleviate issues like leg weakness and fatigue, which stroke survivors often experience. ^{4 5 6 7 8}

Who Is on the Research Team?

Matthew Durand, PhD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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 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]

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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6331204/

Remote ischemic conditioning for stroke: clinical data ... This review focuses on recent advances in clinical studies of RIC in stroke management, its challenges, and the potential directions of future studies.

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.045040

Remote Ischemic Conditioning and Outcomes in Acute ... The primary outcome was excellent functional outcome at 90 days, defined as modified Rankin Scale score of 0 to 1. Compared with patients ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405580825002717

Research progress on remote ischemic conditioning for ... Clinical studies have confirmed that remote ischemic conditioning improves neurological recovery, reduces infarct volume, and enhances prognosis. However, the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10903142/

Remote ischemic conditioning for stroke: A critical ... A recent review demonstrates that animal models of RIC and stroke have repeatedly shown that IC is able to reduce infarct size and improve early neurological ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2795267

Effect of Remote Ischemic Conditioning vs Usual Care on ... In 2012, an estimated 37% of patients had a good prognosis through intravenous thrombolysis, and a 2016 meta-analysis estimated that about 46% ...

6. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.124.048509

Safety and Efficacy of Remote Ischemic Conditioning in ... RIC was safe in patients with acute ischemic stroke who received IVT. However, it did not significantly improve excellent functional outcome.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10401132/

Efficacy and safety of remote ischemic conditioning for acute ... The safety outcomes were RIC‐related adverse events including arm pain assessed by visual scale, redness or swelling of arms, skin petechiae on arms, dizziness ...

8. academic.oup.com academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf570/8232488

the SERIC-EVT trial | European Heart Journal | Oxford Academic This study aimed to assess the efficacy and safety of remote ischaemic conditioning (RIC), a promising neuroprotective treatment, in patients ...