Ischemic Conditioning for Stroke

Overseen By Mark Q Cummings, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Illinois at Chicago

Must not be taking: Antidepressants, Antipsychotics, Anxiolytics, Anticonvulsants

Disqualifiers: Brainstem lesions, Cognitive impairment, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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: 2

Duration: 2 sessions

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether restricting blood flow to the leg can help stroke survivors improve their walking ability. The technique, called ischemic conditioning (or Remote Ischemic Conditioning, RIC), uses a cuff that inflates around the thigh, similar to a blood pressure cuff. Researchers aim to determine if this method can induce positive changes in the brain and enhance walking speed and control. Participants should have experienced a stroke over six months ago and have difficulty walking due to the stroke. As an unphased trial, this study provides a unique opportunity for participants to contribute to innovative research that could enhance rehabilitation techniques for stroke survivors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that could alter brain activity or increase the risk of seizures, like antidepressants or anticonvulsants, you may not be eligible to participate.

What prior data suggests that ischemic conditioning is safe as a neuromodulatory technique for stroke?

Research shows that ischemic conditioning is generally safe, even for those who have had a stroke. Studies have found no serious side effects. Some participants reported mild issues like arm pain, redness, or dizziness, but these were not severe.

Other research suggests that ischemic conditioning can aid recovery after a stroke. It may improve brain function and reduce the affected brain area. This indicates that the treatment could be beneficial without major safety concerns.

Overall, current research suggests that ischemic conditioning is well-tolerated. Prospective trial participants might find this information reassuring regarding its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Ischemic Conditioning is unique because it uses a rapid inflation cuff to temporarily restrict blood flow, creating a protective response in the body. Unlike standard stroke treatments like clot-busting drugs or mechanical thrombectomy, which directly target the blockage, this technique aims to boost the body's natural defense mechanisms. Researchers are excited about its potential to reduce brain damage and improve recovery by conditioning the body to better handle the stress of reduced blood flow during a stroke.

What evidence suggests that ischemic conditioning is effective for improving gait function in stroke?

Research has shown that ischemic conditioning, which involves temporarily cutting off blood flow, can aid recovery after a stroke. Studies indicate that it improves brain recovery and increases blood flow to the brain. It also reduces the amount of brain damage caused by a stroke, leading to better recovery outcomes. Some trials demonstrated improvements in brain function and movement skills, crucial for walking and movement. This trial will compare real ischemic conditioning with sham ischemic conditioning to evaluate its effectiveness in enhancing movement control and walking speed in stroke survivors. ^{3 4 6 7 8}

Who Is on the Research Team?

Sangeetha Madhavan, PT, PhD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-35 who have had a stroke. It's not open to those with other neurological impairments. Participants will undergo sessions of ischemic conditioning and aerobic exercise to see if these can improve their walking ability after the stroke.

Inclusion Criteria

Able to cycle on the recumbent stepper

I had a stroke more than 6 months ago.

I have difficulty walking due to partial paralysis.

Exclusion Criteria

Failure to pass the Physical Activity Readiness Questionnaire (PAR-Q)

I have a neurological condition that affects my movement.

Concussion within the last 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two sessions of ischemic conditioning with measures of brain activity and motor behavior testing before and after each session

2 sessions

2 visits (in-person)

Follow-up

Participants are monitored for changes in corticomotor excitability, ankle motor control, transcallosal inhibition, and lower limb strength

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ischemic Conditioning

Trial Overview The study tests whether restricting blood flow using a cuff on the thigh (ischemic conditioning) or doing aerobic exercise can help change brain activity and enhance motor skills like strength, control, and speed in people recovering from a stroke.

How Is the Trial Designed?

Group I: Ischemic Conditioning Experimental Treatment 1 Intervention

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.

Group II: Sham Ischemic Conditioning Placebo Group 1 Intervention

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.

Ischemic Conditioning is already approved in China for the following indications:

Approved in China as Remote Ischemic Conditioning for:

• Acute ischemic stroke

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

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) 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]

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]

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 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) 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]

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]

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

Effect of Remote Ischemic Conditioning vs Usual Care on ... This randomized clinical trial compares the efficacy of remote ischemic conditioning as an adjunct to guideline-based treatment vs usual ...

4. 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 ...

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

the SERIC-EVT trial | European Heart Journal | Oxford Academic Remote ischaemic conditioning can have a positive effect on cerebral haemodynamics, and this premise is the cerebral artery reperfusion.

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. 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 ...