Improve PAD PERformance With METformin

NCT03054519 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: STU00203784
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 5

Brief Summary

The PERMET trial will determine whether metformin daily for six months improves six-minute walk performance in individuals with peripheral artery disease compared to placebo.

Conditions

Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Six-minute walk performance

  Participants walking up and down a 100 foot hallway for six minutes following a standardized protocol. The goal is for them to walk as far as possible in six minutes

  Change from baseline to six-month follow-up

Secondary Outcomes (5)

• Maximal treadmill walking time

  Change from baseline to six-month follow-up

• Brachial artery flow-mediated dilation

  Change from baseline to six-month follow-up

• The Walking Impairment Questionnaire

  Change from baseline to six-month follow-up

• The SF-36 Physical Functioning Score

  Change from baseline to six-month follow-up

• Calf muscle biopsy biochemical measures

  Change from baseline to six-month follow-up

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Metformin daily

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo daily for six months.

Drug: Placebo

Interventions

Metformin DRUG

Participants will be prescribed up to 2,000 mgs daily of metformin

Metformin

Placebo DRUG

Placebo pills will appear identical to the metformin to maintain blinding of participants and investigators.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants will have PAD. PAD will be defined as follows:
• Second, potential participants who have an ABI \> 0.90 but ≤ 1.00 and experience a 20% or higher drop in ABI after heel-rise exercise will be eligible.
• Third, potential participants with an ABI \> 0.90 who have vascular lab evidence of PAD or angiographic evidence of PAD who have ischemic symptoms during the six-minute walk and/or treadmill exercise stress test will be eligible.
• Fourth, potential participants with a history of lower extremity revascularization who do not meet the criterion above and have an ABI \> 0.90 with a 20% or higher drop in ABI after heel-rise exercise will be eligible.

You may not qualify if:

• Above- or below-knee amputation.
• Critical limb ischemia.
• Wheelchair-bound or requiring a walker to ambulate.
• Walking is limited by a symptom other than PAD.
• Current foot ulcer on bottom of foot.
• Diabetes mellitus defined as one or more of a) patient report of physician diagnosed diabetes mellitus, b) use of one or more diabetes medications, c) two baseline hemoglobinA1C values of \>6.5, d) two fasting glucose values \>126 mg/dl. \[NOTE: the second fasting glucose value and hemoglobin A1C values will be at the discretion of the principal investigator. For example, if the first glucose value is \>300 or the first A1C value is \>6.9, then investigators may decide not to repeat the value.\]
• Chronic kidney disease defined as GFR \<=45. \[NOTE: if GFR is 40-44, investigator discretion will be used to determine if a repeat test may be performed. If the second GFR value is \>45, the participant may be included.\]
• Chronic liver disease defined as two or more hepatic function tests \>=2.0 times the upper limit of normal. \[NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.\]
• Failure to successfully complete the 2-week study run-in, defined as unable to tolerate metformin and/or failing to take the medication daily for 10 or more days in the two-week period.
• Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months.
• Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
• Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score \<23 or dementia. However, investigator discretion may be used to allow some people below this threshold to participate, if the investigator determines there is another reason for their lower score, including lack of familiarity with the English language or lack of sufficient education to achieve a score of 23 or higher. Note that the MMSE include some spelling and English writing proficiency.
• Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
• Currently taking metformin or has taken metformin in past six months.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (5)

University of Florida

Gainesville, Florida, 32610, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Related Publications (2)

• McDermott MM, Domanchuk KJ, Tian L, Zhao L, Zhang D, Bazzano L, Berceli S, Criqui MH, Ferrucci L, Guralnik JM, Leeuwenburgh C, Ho KJ, Ismaeel A, Kibbe MR, Korcarz C, Kosmac K, Lloyd-Jones D, Peterson CA, Stein JH, Sufit R, Wilkins J, Polonsky TS. Metformin to Improve Walking Performance in Lower Extremity Peripheral Artery Disease: The PERMET Randomized Clinical Trial. JAMA. 2026 Feb 3;335(5):407-415. doi: 10.1001/jama.2025.21358.

  PMID: 41205146 RESULT

• Nayak P, Polonsky T, Tian L, Greenland P, Xu S, Zhang D, Zhao L, Criqui MH, Kibbe MR, Gladders B, Goodney P, Ho K, Guralnik JM, McDermott MM. Medical therapies, comorbid conditions, and functional performance in people with peripheral artery disease enrolled in clinical trials between 2004 and 2021. Vasc Med. 2023 Apr;28(2):144-146. doi: 10.1177/1358863X221145533. Epub 2023 Jan 1.

  PMID: 36588397 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Metformin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Mary McDermott, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at Northwestern University Feinberg School of Medicine

Study Record Dates

• First Submitted: February 13, 2017
• First Posted: February 15, 2017
• Study Start: May 23, 2017
• Primary Completion: August 20, 2025
• Study Completion: November 1, 2025
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)