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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to see how small blood vessels respond to the stress of high intensity exercise, and if a safe and simple intervention called ischemic conditioning can protect blood vessels from the stress of exercise. Participants will come in for 3 study visits and get home-based ischemic conditioning. At Study Visit 1, participants will be assessed for their frailty and physical function. Afterwards, they will perform an exercise test. At Study Visit 2, patients will undergo 2 microvascular assessments, perform a high-intensity exercise, then undergo the same 2 microvascular assessments again. Participants will be given a handheld sphygmomanometer and a blood pressure cuff to take home. Depending on which group the participants get randomized into, participants will place the blood pressure cuff around their non-dominant upper arm and inflate to either a low or high pressure for 2 weeks at home. Participants will repeat the same steps in Study Visit 2 for Study Visit 3. In addition, participants will also be assessed for their frailty and physical function.

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.

How is the treatment Ischemic Conditioning different from other treatments for frailty?

Ischemic Conditioning is unique because it involves temporarily restricting blood flow to a limb to protect other parts of the body, like the heart, from damage. This method is different from typical treatments as it uses the body's natural response to stress to potentially improve health outcomes. ^{1 2 3 4 5}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Remote Ischemic Conditioning in Patients with Acute Coronary Syndromes: A Systematic Review with Meta-Analysis and Trial Sequential Analysis. [2022]

2. United States 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. [2011]

3. England pubmed.ncbi.nlm.nih.gov

Daily remote ischaemic conditioning following acute myocardial infarction: a randomised controlled trial. [2019]

4. Netherlands 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. [2015]

5. Germany pubmed.ncbi.nlm.nih.gov

[Cardioprotection via the arm? : How a blood pressure cuff decreases infarct sizes]. [2019]