Ischemic Preconditioning for Lower Extremity Amputation

Overseen By Lindsay Slater

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Illinois at Chicago

Disqualifiers: Neurological disorder, Uncontrolled hypertension, Heart failure, others

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

Compensation: Varies

Number of Visits: 7

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how ischemic preconditioning, a technique using a blood pressure cuff on the leg, might improve thigh strength and walking ability. The trial includes two groups: one using low pressure and the other using high pressure. Individuals who have had a leg amputation for more than two years and can walk independently without aids may qualify. Participants must have a safe, wound-free prosthetic limb. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance mobility and quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot start new medications or change the dosage of medications that could affect your walking, balance, or heart function during the study.

What prior data suggests that ischemic preconditioning is safe for improving thigh strength and walking ability?

Research has shown that ischemic preconditioning, a technique using a blood pressure cuff to briefly reduce blood flow, has been tested for safety in several studies. One study with pigs demonstrated that this method significantly lowered inflammation and lung damage, suggesting potential protective effects.

Another study examined individuals with type 2 diabetes and found that it helped protect against severe damage from reduced blood flow, supporting its potential safety and benefits in humans. Additionally, research on people with diabetic foot ulcers indicated that ischemic preconditioning might lower the risk of amputations without causing serious side effects.

These findings suggest that ischemic preconditioning is generally well-tolerated. However, discussing any concerns with the study team or a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ischemic preconditioning for lower extremity amputation because it's a non-invasive technique that could help improve outcomes after surgery. Unlike traditional treatments that focus on managing complications post-surgery, this method aims to protect tissues before damage occurs by temporarily restricting and restoring blood flow using a blood pressure cuff. The trial explores two approaches: a low-pressure and a high-pressure regimen, both designed to trigger the body's natural protective responses. This innovative approach could reduce surgical risks and enhance recovery, offering a proactive way to tackle challenges associated with amputations.

What evidence suggests that ischemic preconditioning could be effective for improving thigh strength and walking ability?

This trial will compare two approaches to ischemic preconditioning for lower extremity amputation. Research has shown that ischemic preconditioning, which uses a blood pressure cuff to temporarily cut off blood flow, might aid muscle recovery and performance. However, results are mixed. Some studies suggest it could enhance blood vessel function, while others have not found significant benefits for certain outcomes. For instance, a review of several studies found little improvement in key areas like overall physical performance. More research is needed to determine its effects on thigh strength and walking ability. ^{6 7 8 9 10}

Who Is on the Research Team?

Lindsay Slater

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

This trial is for adults over 18 who have had one lower limb amputated above the knee at least two years ago. Participants must be able to walk independently with a prosthetic limb for at least 10 minutes and should not have any open wounds on their limbs.

Inclusion Criteria

My prosthetic limb is durable and safe for study activities.

I can walk on my own without any help or devices.

It has been over two years since my leg was amputated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ischemic preconditioning with a blood pressure cuff on the intact limb, either at low or high pressure, every other day for 7 sessions over 14 days

2 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of leg strength, arterial stiffness, and gait

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ischemic Preconditioning

Trial Overview

The study is examining if applying a blood pressure cuff to the leg can improve thigh muscle strength and walking ability in individuals with an above-knee amputation.

How Is the Trial Designed?

Group I: Ischemic Preconditioning at High Pressure Active Control 1 Intervention

In this arm, the participant will receive ischemic preconditioning (a blood pressure cuff on the intact limb) inflated to 225mmHg for 5 minutes followed by 5 minutes of reperfusion on a cycle for a total of 50 minutes. This will be completed every other day for 7 session (14 days).

Group II: Ischemic Preconditioning at Low Pressure Placebo Group 1 Intervention

In this arm, the participant will receive ischemic preconditioning (a blood pressure cuff on the intact limb) inflated to 25mmHg for 5 minutes followed by 5 minutes of reperfusion on a cycle for a total of 50 minutes. This will be completed every other day for 7 session (14 days).

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 preconditioning (RIPC) significantly increased the ankle-brachial index (ABI) in diabetic patients with peripheral arterial disease, demonstrating its potential as a protective intervention against ischemia.

In a randomized trial with 60 participants, the RIPC group showed a notable increase in ABI from 0.82 to 0.86 after the intervention, indicating improved blood flow, while the control group did not show significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated Remote Ischemic Conditioning Effect on Ankle-brachial Index in Diabetic Patients - A Randomized Control Trial. Shahvazian, N., Rafiee, M., Rahmanian, M., et al.[2020]

Remote ischemic preconditioning (RIPC) significantly improved the initial claudication distance in patients with intermittent claudication, suggesting it enhances muscle tissue resistance to ischemia.

Despite the improvement in initial claudication distance, RIPC did not have an effect on the total walking distance of the patients, indicating that while it may help with short-term performance, it does not extend overall walking capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote ischemic preconditioning in patients with intermittent claudication. Saes, GF., Zerati, AE., Wolosker, N., et al.[2022]

Limb remote ischemic postconditioning (RIPostC) applied early during reperfusion significantly reduced brain injury and improved neurological function in a rat model of cerebral ischemia.

The study found that RIPostC enhances autophagy in brain cells through the AKT/GSK3β pathway, which is crucial for reducing cell death after ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AKT/GSK3β-dependent autophagy contributes to the neuroprotection of limb remote ischemic postconditioning in the transient cerebral ischemic rat model. Qi, ZF., Luo, YM., Liu, XR., et al.[2021]

In a study of 63 patients with intermittent claudication, those who underwent remote ischemic preconditioning (RIPC) showed significant improvements in walking capacity, with increases in initial claudication distance (ICD) and total walking distance (TWD) after four weeks of treatment.

Patients receiving RIPC also experienced a notable decrease in the time to relief of claudication (TRC), indicating that RIPC effectively enhances muscle resistance to ischemia and improves functional ability in patients with peripheral artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Repeated Remote Ischemic Preconditioning on Peripheral Arterial Disease in Patients Suffering from Intermittent Claudication. Balin, M., Kıvrak, T.[2022]

Remote ischemic preconditioning (RIPC) significantly improved maximal swim performance in national-level swimmers, with a mean improvement of 0.7 seconds in 100 m swim time and a 1.1% improvement relative to personal best times, based on a study involving 34 athletes.

RIPC was shown to release a protective factor that reduced heart tissue damage in mice, indicating a potential mechanism for its benefits, although it did not significantly affect submaximal exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote preconditioning improves maximal performance in highly trained athletes. Jean-St-Michel, E., Manlhiot, C., Li, J., et al.[2022]

A meta-analysis of 13 randomized controlled trials involving 1,097 patients found that remote ischemic preconditioning (RIPC) did not significantly reduce mortality or improve renal or cardiac outcomes in patients undergoing vascular surgery.

The study suggests that RIPC may not provide any benefits in this context, indicating a need for further large-scale trials to explore its efficacy in major vascular surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of remote ischemic preconditioning for vascular surgery. Stather, PW., Wych, J., Boyle, JR.[2020]

Remote ischemic preconditioning (RIPC) effectively protects against brain damage from stroke in a rat model, preserving neurological function three days after ischemic injury.

RIPC induces significant immune changes, including increased levels of protective immune cells like B cells and noninflammatory monocytes, while also enhancing cytokine responses, suggesting a mechanism for its neuroprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses. Liu, ZJ., Chen, C., Li, XR., et al.[2020]

In a study involving 18 male pigs, ischemic preconditioning (IPC) significantly reduced markers of systemic inflammation and acute lung injury following prolonged limb ischemia and reperfusion, indicating its protective effects.

Pigs that underwent IPC before ischemia showed lower levels of interleukin-6 and reduced pulmonary edema and respiratory failure compared to those that did not receive IPC, highlighting its potential as a therapeutic strategy in managing ischemic injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury. Harkin, DW., Barros D'Sa, AA., McCallion, K., et al.[2020]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10084674/

Efficacy of remote ischaemic preconditioning on outcomes ...

This meta-analysis did not show an improvement in the primary outcomes of interest with the use of RIPC. RIPC was associated with a small ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10808809/

The effects of lower limb ischaemic preconditioning

This review focuses on the physiological responses for VO 2max, haemoglobin, metabolic and genetic responses to various IPC interventions.

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S1078588419304940

Effects of Remote Ischaemic Preconditioning on Arterial ...

The aim of this study was to evaluate the effect of RIPC on arterial stiffness in patients with peripheral arterial disease (PAD) undergoing lower limb DSA.

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1078588421005384

Deleterious Effects of Remote Ischaemic Per-conditioning ...

The aim of this study was to investigate whether remote ischaemic per-conditioning might protect skeletal muscle during lower limb ischaemia–reperfusion (IR).

5.

researchgate.net

researchgate.net/publication/336705835_Effects_of_Remote_Ischaemic_Preconditioning_on_Arterial_Stiffness_in_Patients_Undergoing_Lower_Limb_Angiographic_Procedures_A_Randomised_Clinical_Trial

Effects of Remote Ischaemic Preconditioning on Arterial ...

RIPC has been shown to reduce myocardial and renal injury but its effect on arterial stiffness in patients undergoing lower limb digital subtraction angiography ...

6.

withpower.com

withpower.com/trial/phase-amputation-traumatic-8-2023-49fa0

Ischemic Preconditioning for Lower Extremity Amputation

In a study involving 18 male pigs, ischemic preconditioning (IPC) significantly reduced markers of systemic inflammation and acute lung injury following ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5018170/

Remote ischaemic conditioning in the context of type 2 ...

This technique induces short periods of ischaemia that have been found to protect against a more significant ischaemic insult. Remote ischaemic ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02635347

Remote Ischemic Conditioning (RIC) in Recipients of Brain ...

This study will assess the feasibility of lower limb-ischemia induced Remote Ischemic Conditioning (RIC) in the perioperative period before, during, ...

9.

ahajournals.org

ahajournals.org/doi/10.1161/JAHA.118.011779

Efficacy of Long‐Term Remote Ischemic Conditioning on ...

Primary outcome was transcutaneous tissue oxygen tension of the instep of the feet. Secondary outcomes were aortic pulse wave velocity, toe ...

10.

aetna.com

aetna.com/cpb/medical/data/800_899/0814.html

Remote Ischemic Conditioning - Medical Clinical Policy ...

Regulski and colleagues (2021) noted that patients with a diabetic foot ulcer (DFU) suffer disabilities and are at increased risk for lower extremity amputation ...