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Peripheral Artery DiseasePhase 3PERMETNCT03054519

Improve PAD PERformance With METformin

A Phase 3 study testing Metformin in people with Peripheral Artery Disease, run by Northwestern University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Peripheral Artery Disease
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
202 participants
Where
5 sitesUnited States
Study dates
23 May 2017to 1 Nov 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All participants will have PAD. PAD will be defined as follows:
  • First, an ankle brachial index (ABI) <=0.90 at the baseline study visit is an inclusion criterion for PAD.
  • 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.

Who cannot join

  • 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.]
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  • 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.
  • Increase in angina or angina at rest
  • Non-English speaking.
  • Visual impairment that limits walking ability.
  • In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.
  • Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) and adults unable to consent will not be included in the study.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • University of Florida

    Gainesville, Florida, 32610

  • Tulane University

    New Orleans, Louisiana, 70112

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

Other trials in United States

About this study

Official title: Improve PAD Performance With Metformin: The PERMET Trial

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.

Being tested
Metformin, Placebo
Medical subject headings
Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

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

  • PlaceboDrug

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

Study groups in NCT03054519
Study groupRoleWhat they receive
MetforminActive comparatorMetformin daily
Receives: Drug: Metformin
PlaceboPlacebo comparatorPlacebo daily for six months.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Change from baseline to six-month follow-up

Secondary outcomes (5)

  1. Maximal Treadmill Walking Time

    A Gardner treadmill exercise protocol will be used

    Measured: Change from baseline to six-month follow-up

  2. Brachial Artery Flow-mediated Dilation

    Upper brachial artery flow-mediated dilation was evaluated by measuring percent change in the brachial artery diameter in response to reactive hyperemia, induced by inflating a blood pressure cuff for five minutes over the brachial artery.

    Measured: Percent change from baseline to six-month follow-up

  3. The Walking Impairment Questionnaire - Distance Score

    The Walking impairment questionnaire is a patient reported outcome measure, in which participants indicate the ease of walking distances ranging from across the room to up to approximately 1500 feet. The score is calculated on a 0-100 scale, where 0 indicates the in ability to walk any of the distances and 100 indicates no difficulty walking any of the distances.

    Measured: Change from baseline to six-month follow-up

  4. The SF-36 Physical Functioning Score

    This outcome is a patient reported quality of life measure. The score ranges from 0 to 100, where 0 indicates extremely poor functioning and 100 indicates the best possible functioning,

    Measured: Change from baseline to six-month follow-up

  5. Calf Muscle Biopsy Biochemical Measures - Capillary Density

    Capillary density was measured as the number of capillaries per mm2 of muscle.

    Measured: Change from baseline to six-month follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2017
  2. Study start23 May 2017
  3. Primary completion20 Aug 2025
  4. Study completion1 Nov 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03054519
Sponsor's protocol ID
STU00203784
Acronym
PERMET
Status last verified
Jul 2026
First submitted
13 Feb 2017
Last updated
24 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 41205146

  • McDermott MM, Cetlin MD, Domanchuk KJ, Xu S, Whipple MO, Polonsky T, Criqui MH, Guralnik JM, Tian L, Zhao L, Ho KJ, Greenland P, Treat-Jacobson D. Community-based recruitment with ankle brachial index testing to identify peripheral artery disease participants for randomized clinical trials. Am Heart J. 2026 Oct;300:107450. doi: 10.1016/j.ahj.2026.107450. Epub 2026 Apr 24.

    PubMed 42035974

  • 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.

    PubMed 36588397

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Peripheral Artery Disease, run by Northwestern University at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Six-minute Walk Performance (time frame: Change from baseline to six-month follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03054519, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.

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Improve PAD PERformance With METformin (NCT03054519) | AzTrials