Ischemic Conditioning for Frailty

Overseen By Jennifer Nguyen

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Myocardial infarction, Morbid obesity, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether a simple method called ischemic conditioning (also known as Remote Ischemic Conditioning or RIC) can protect small blood vessels during high-intensity exercise. Participants will use a blood pressure cuff at home to apply varying pressure levels to their arm, helping researchers assess the technique's effectiveness for individuals with frailty. The trial compares low and high pressure groups to determine which offers more protection. It may suit those aged 65 to 85 who feel frail but can still engage in high-intensity exercise. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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.

Is there any evidence suggesting that ischemic conditioning is likely to be safe?

Research has shown that ischemic conditioning is generally safe. Studies have found that short-term remote ischemic conditioning does not harm the body. In fact, it can reduce the risk of major issues, such as heart or brain problems, and aid recovery in some cases. These studies reported no serious side effects, suggesting the treatment is well-tolerated. However, monitoring for any possible reactions during treatment remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ischemic conditioning for frailty because it offers a novel approach that differs significantly from current treatments like exercise programs and nutritional supplements. Ischemic conditioning involves using a blood pressure cuff to temporarily reduce blood flow to an arm, which may trigger the body to strengthen its resilience and improve overall physical function. This method is non-invasive and can be easily administered at home, which makes it an accessible option for many individuals. Moreover, the trial explores two different intensities—low and high—potentially providing insights into optimizing the treatment's effectiveness.

What evidence suggests that ischemic conditioning could be effective for frailty?

Research shows that ischemic conditioning can improve blood vessel function. Studies suggest it might protect the heart and brain by reducing the risk of heart attacks and strokes. Short-term use has been linked to improved blood flow and healthier blood vessels. Some research also indicates it could enhance brain function, particularly for individuals with existing blood vessel issues. In this trial, participants will be randomized into either the Ischemic Conditioning-Low or Ischemic Conditioning-High group to evaluate its potential in managing frailty by supporting healthier blood vessels. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for men and women aged 65-85 who may be experiencing frailty or have poor blood vessel function. Participants should be able to perform high-intensity exercise and commit to three study visits along with home-based treatments using a blood pressure cuff.

Inclusion Criteria

I am between 65 and 85 years old.

Exclusion Criteria

I have had blood clots in my arms or legs.

My high blood pressure is not under control.

My BMI is over 40.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete assessments on frailty and physical function and perform an exercise test

1 day

1 visit (in-person)

Treatment

Participants undergo microvascular assessments, perform high-intensity exercise, and engage in home-based ischemic conditioning for 2 weeks

2 weeks

2 visits (in-person), daily home-based intervention

Follow-up

Participants are monitored for changes in microvascular function and frailty after treatment

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ischemic Conditioning

Trial Overview The trial tests ischemic conditioning, which involves temporarily restricting blood flow with a cuff, to see if it can protect small blood vessels from stress during high-intensity exercise in older adults.

How Is the Trial Designed?

Group I: Ischemic Conditioning-High Experimental Treatment 1 Intervention

We will use a randomized block design to randomize individuals into either Ischemic Conditioning-Low or Ischemic Conditioning-High group using an online randomizer. A handheld sphygmomanometer and blood pressure cuff will be given to study participants. For the Ischemic Conditioning-High group participants, while sitting, the cuff will be placed around the non-dominant upper arm and inflated to 225 mmHg for 5 min, then released for a 5-min recovery period. A 5-min inflation period is most used. Five cycles of inflation/recovery will be performed. All participants will perform the intervention daily for 2 weeks. Participants will complete daily log sheets documenting the time and pressure of each cuff inflation.

Group II: Ischemic Conditioning-Low Placebo Group 1 Intervention

We will use a randomized block design to randomize individuals into either Ischemic Conditioning-Low or Ischemic Conditioning-High group using an online randomizer. A handheld sphygmomanometer and blood pressure cuff will be given to study participants. For the Ischemic Conditioning-Low group participants, while sitting, the cuff will be placed around the non-dominant upper arm and inflated to 10 mmHg for 5 min, then released for a 5-min recovery period. A 5-min inflation period is most used. Five cycles of inflation/recovery will be performed. All participants will perform the intervention daily for 2 weeks. Participants will complete daily log sheets documenting the time and pressure of each cuff inflation.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

A systematic review of 13 randomized clinical trials involving 7183 patients found that remote ischemic conditioning (RIC) did not significantly reduce mortality rates in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) over a median follow-up of 1 year.

RIC also showed no significant effect on the incidence of myocardial infarction (MI) or congestive heart failure (CHF), indicating that this intervention may not provide the expected clinical benefits in these patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning in Patients with Acute Coronary Syndromes: A Systematic Review with Meta-Analysis and Trial Sequential Analysis. Sandven, I., Eritsland, J., Abdelnoor, M.[2022]

A single episode of remote ischemic conditioning during coronary occlusion significantly reduces heart tissue damage (infarct size) after a heart attack, as shown in rat models.

Repeated remote postconditioning therapy enhances protection against heart remodeling and improves long-term survival rates, suggesting a potential clinical benefit for patients experiencing myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated remote ischemic postconditioning protects against adverse left ventricular remodeling and improves survival in a rat model of myocardial infarction. Wei, M., Xin, P., Li, S., et al.[2011]

Remote ischemic conditioning (RIC) significantly improves left ventricular ejection fraction (LVEF) and prevents deterioration of diastolic function in rats after myocardial infarction, despite similar heart attack sizes between treated and untreated groups.

RIC treatment reduces heart tissue fibrosis and oxidative stress, potentially through the upregulation of microRNA-29a and insulin-like growth factor 1 receptor (IGF-1R), indicating a mechanism of action involving exosome-mediated communication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction. Yamaguchi, T., Izumi, Y., Nakamura, Y., et al.[2015]

In a study involving 73 patients with impaired left ventricular ejection fraction (LVEF) after a heart attack, daily remote ischaemic conditioning (rIC) for 4 weeks did not lead to any significant improvement in LVEF compared to a control group.

No differences were observed in secondary outcomes, such as infarct size or major adverse cardiac events, indicating that rIC may not provide additional benefits post-myocardial infarction in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial. Vanezis, AP., Arnold, JR., Rodrigo, G., et al.[2019]

Remote ischemic conditioning (RIC) is a promising technique that may protect the heart from damage caused by ischemia/reperfusion injury during myocardial infarctions, but the exact mechanisms are still not fully understood.

While RIC has been studied extensively in laboratory settings, there is a lack of large clinical trials assessing its impact on mortality rates in patients, highlighting a gap in current research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardioprotection via the arm? : How a blood pressure cuff decreases infarct sizes]. Haller, PM., Kiss, A., Wojta, J., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12539847/

Short-term effects of remote ischemic conditioning on vascular ... This systematic review and meta-analysis found that short-term remote ischemic conditioning was associated with improvements in endothelial ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.075254

The PRINCE Randomized Clinical Trial | Circulation Remote ischemic preconditioning (RIPC) was reported to decrease these complication rates. However, such supportive evidence lacks robustness.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0031938422001998#!

Effects of remote ischemic conditioning on cognitive ... Long-term daily RIC treatment may improve cognitive function after 6- 12 months in patients with pre-existing cerebrovascular disease. The ...

4. aging-us.com aging-us.com/article/101527/text

Remote ischemic conditioning: a promising therapeutic ... Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart ...

5. ccforum.biomedcentral.com ccforum.biomedcentral.com/articles/10.1186/s13054-023-04786-y

Remote ischemic conditioning reduces adverse events in ... Treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38167175/

Remote ischemic conditioning reduces adverse events in ... Treatment with remote ischemic conditioning decreased the major adverse cardiac and cerebrovascular events and improved functional outcomes at 90 days.