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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the relationship between thigh strength and walking ability and assess if using a blood pressure cuff on the leg improves strength and walking performance.

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 data supports the effectiveness of the treatment Ischemic Preconditioning for Lower Extremity Amputation?

Research shows that remote ischemic preconditioning (RIPC), which involves short periods of reduced blood flow, can protect muscles and other organs from damage due to lack of blood flow. Studies have found that RIPC can improve walking ability in patients with peripheral artery disease and may protect against injury in other organs, suggesting it could be beneficial for lower extremity amputation. ^{1 2 3 4 5}

Is remote ischemic preconditioning (RIPC) safe for humans?

Remote ischemic preconditioning (RIPC) has been studied in various conditions, including peripheral artery disease and stroke, and is generally considered safe in humans. It involves temporarily restricting blood flow to a limb to protect other parts of the body from damage when blood flow is restored. ^{1 3 5 6 7}

How is ischemic preconditioning different from other treatments for lower extremity amputation?

Ischemic preconditioning (IPC) is unique because it involves applying short, controlled periods of reduced blood flow to one area of the body to protect another area from damage due to lack of blood flow. This approach is different from other treatments as it uses the body's natural protective mechanisms rather than drugs or surgery. ^{1 2 4 5 8}

Research Team

Lindsay Slater

Principal Investigator

University of Illinois at Chicago

Eligibility Criteria

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 am 18 years old or older.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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) 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]

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) 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]

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]

References

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

Remote ischemic preconditioning in patients with intermittent claudication. [2022]

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

Ischemic preconditioning before lower limb ischemia--reperfusion protects against acute lung injury. [2020]

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

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

4. India pubmed.ncbi.nlm.nih.gov

Repeated Remote Ischemic Conditioning Effect on Ankle-brachial Index in Diabetic Patients - A Randomized Control Trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Remote Ischemic Preconditioning-Mediated Neuroprotection against Stroke is Associated with Significant Alterations in Peripheral Immune Responses. [2020]

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

A systematic review and meta-analysis of remote ischemic preconditioning for vascular surgery. [2020]

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

Remote preconditioning improves maximal performance in highly trained athletes. [2022]

8. England 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. [2021]