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

50 Participants Needed

Trial Summary

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 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 the treatment ischemic conditioning unique for stroke?

Ischemic conditioning is unique because it is a noninvasive treatment that involves temporarily restricting blood flow to a limb (like using a blood pressure cuff) to protect the brain during a stroke. Unlike other treatments that directly target the brain, this method works remotely and can be used alongside standard therapies like clot-busting drugs or surgical procedures. ^{2 6 7 8 9}

What is the purpose of this trial?

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: * Can ischemic conditioning produce neuromodulatory changes in the lower limb primary motor cortex? * Can ischemic conditioning be used as a neuromodulatory technique to improve strength, motor control, and gait speed in individuals with stroke when compared to sham ischemic conditioning? 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 or sham). Each participant will experience measures of brain activity and motor behavior testing before and after both sessions (ischemic conditioning and sham ischemic conditioning). 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.

Research Team

Sangeetha Madhavan, PT, PhD

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

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

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

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

5. 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]

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]