What side effects are associated with this type of intervention?

Common treatments for Peripheral Arterial Disease (PAD) include Metformin, which can cause gastrointestinal issues such as nausea, vomiting, diarrhea, and abdominal discomfort. Statins, used to manage cholesterol, may lead to muscle pain, liver enzyme abnormalities, and rarely, rhabdomyolysis. Antiplatelet agents like aspirin can result in gastrointestinal bleeding and ulcers. Cilostazol, a phosphodiesterase inhibitor, may cause headaches, diarrhea, and palpitations. Exercise therapy, while generally safe, can cause muscle soreness or injury if not properly supervised.

What prior FDA approvals exist?

FDA-approved treatments for Peripheral Arterial Disease (PAD) that focus on improving endothelial function and reducing inflammation include cilostazol and statins. Cilostazol, a phosphodiesterase inhibitor, has been shown to improve symptoms of intermittent claudication by increasing blood flow to the limbs. Statins, such as atorvastatin and simvastatin, are primarily used for lipid-lowering but also have anti-inflammatory properties and have been shown to improve walking distance and reduce cardiovascular events in PAD patients. These treatments are somewhat similar to metformin, which is being studied for its potential benefits in improving endothelial function and reducing inflammation in PAD patients.

What other types of research exist?

Promising novel alternatives to Metformin for PAD patients include Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide and semaglutide. These agents have shown benefits in reducing inflammation and improving endothelial function. Additionally, PCSK9 inhibitors like evolocumab have demonstrated significant cardiovascular benefits and may also be considered.

← Back to Search

Anti-diabetic agent

Metformin for Peripheral Arterial Disease (PERMET Trial)

Q: What is the mechanism of action of this treatment?

Peripheral Arterial Disease (PAD) treatments aim to improve blood flow and reduce symptoms such as claudication. Common treatments include exercise therapy, which enhances muscle efficiency and circulation, and pharmacologic therapies like statins and cilostazol. Statins lower cholesterol, reducing plaque buildup in arteries, while cilostazol improves blood flow by inhibiting platelet aggregation and dilating blood vessels. Metformin, being studied in the PERMET trial, may improve endothelial function and reduce inflammation, potentially enhancing walking performance in PAD patients. These mechanisms are crucial as they address the underlying vascular issues and improve quality of life.

Phase 3

Recruiting

Led By Mary McDermott, MD

Research Sponsored by Northwestern University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants with a history of lower extremity revascularization and ABI > 0.90 with a 20% or higher drop in ABI after heel-rise exercise

Participants with PAD defined as ABI <=0.90 at the baseline study visit

Must not have

Current foot ulcer on bottom of foot

Non-English speaking

Timeline

Screening 3 weeks

Treatment Varies

Follow Up change from baseline to six-month follow-up

Awards & highlights

Pivotal Trial

Summary

This trial will test if taking metformin daily can help people with peripheral artery disease walk better by improving their blood flow and reducing inflammation. Metformin has been studied for its potential benefits in improving endothelial function and reducing inflammation in various conditions, including type 2 diabetes and peripheral artery disease.

Who is the study for?

This trial is for individuals with Peripheral Arterial Disease (PAD). Eligible participants may have had lower extremity revascularization, an Ankle-Brachial Index (ABI) of ≤0.90, or a significant drop in ABI after exercise indicating PAD. Exclusions include those planning major surgeries, with severe illnesses like advanced cancer or lung disease requiring oxygen, dementia, recent heart issues, non-English speakers, amputations above/below the knee, wheelchair users or walker dependence.

What is being tested?

The PERMET trial is testing if taking metformin daily for six months can improve walking performance over a six-minute period compared to a placebo in people with PAD. Participants will be randomly assigned to either receive metformin or a placebo and their walking ability will be measured.

What are the potential side effects?

Metformin may cause side effects such as digestive upset including nausea and diarrhea; it might also affect blood sugar levels leading to hypoglycemia especially in diabetic patients not included in this study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I had surgery to improve blood flow in my legs and my ankle-brachial index drops significantly after exercise.

Select...

My ankle-brachial index (ABI) is 0.90 or lower.

Select...

I have leg artery disease with symptoms during physical tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a current ulcer on the bottom of my foot.

Select...

I do not speak English.

Select...

My vision problems make it hard for me to walk.

Select...

I have had an amputation above or below the knee.

Select...

I do not have major illnesses like severe kidney, lung disease, Parkinson's, or any life-threatening condition expected to shorten my life to less than six months.

Select...

My chest pain has gotten worse or I have chest pain even when resting.

Select...

I use a wheelchair or walker to move around.

Select...

I have been diagnosed with chronic kidney disease.

Select...

I have severe blockage in my leg arteries causing pain and ulcers.

Select...

My walking is limited due to a reason other than peripheral artery disease.

Select...

I have a long-term liver condition.

Select...

I have been diagnosed with diabetes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ change from baseline to six-month follow-up

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~change from baseline to six-month follow-up

This trial's timeline: 3 weeks for screening, Varies for treatment, and change from baseline to six-month follow-up for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Six-minute walk performance

Secondary study objectives

Brachial artery flow-mediated dilation

Calf muscle biopsy biochemical measures

Maximal treadmill walking time

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: MetforminActive Control1 Intervention

Metformin daily

Group II: PlaceboPlacebo Group1 Intervention

Placebo daily for six months.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Peripheral Arterial Disease (PAD) treatments aim to improve blood flow and reduce symptoms such as claudication. Common treatments include exercise therapy, which enhances muscle efficiency and circulation, and pharmacologic therapies like statins and cilostazol. Statins lower cholesterol, reducing plaque buildup in arteries, while cilostazol improves blood flow by inhibiting platelet aggregation and dilating blood vessels. Metformin, being studied in the PERMET trial, may improve endothelial function and reduce inflammation, potentially enhancing walking performance in PAD patients. These mechanisms are crucial as they address the underlying vascular issues and improve quality of life.

Molecular mechanisms of vascular dysfunction and cardiovascular biomarkers in type 2 diabetes.