A Phase 3 interventional study of Metformin ER and placebo in Intermittent Claudication, sponsored by VA Office of Research and Development. Recruiting at 1 site in United States. Open to participants aged 35 Years to 89 Years. Per ClinicalTrials.gov, last updated 2026-04-21.
Sponsored by VA Office of Research and Development · Phase 3, Interventional, and Treatment
Peripheral arterial disease (PAD) affects over 20% of aged adults and is very common among Veterans due significant tobacco use. PAD is due to the progressive blockage of peripheral arteries, predominantly to the legs, and results in intermittent claudication (IC) or recurrent muscle pain with activity secondary to insufficient blood supply. Those with PAD and IC experience a progressive decline in walking and poor quality of life. There is no effective medical treatment for PAD and IC. Metformin is a safe and effective treatment for Type 2 diabetes but it can also reduce inflammation, oxidative stress, and improve energy requirements as well as improve blood flow to the legs. Therefore, the investigators will test the ability of Metformin to improve overall functional status, reduce PAD progression, and reduce systemic inflammation in Veterans suffering from PAD and IC in a randomized, placebo controlled trial: Metformin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC) Trial. The success of this trial may identify a safe and effective treatment for PAD and IC.
This is a quadruple blinded randomized controlled trial. Therefore, the allocation of participants to either placebo or metformin is unknown by the participant, research personnel, investigator, or blinded statistician. A total of 200 participants will be randomized over the course of 3 years. Study drug is administered to participants after all inclusion and no exclusion criteria is confirmed, informed consent is completed, and they are randomized. Study drug is continued throughout for 6 months following randomization. Participants are prospectively observed and monitored for 12 months after randomization. The patients' involvement (study visits/study phone calls) will last 12 months. Then, for 5 years, the study team will do a medical chart review as outlined in the ICF and protocol. All main study endpoints are within the 12-month time point. Secondary endpoints including MACE and MALE - major adverse cardiac and major adverse limb events - are time to event end points which can continue beyond the 12-month study time frame and will inform not only the effect of metformin on IC but also the natural history of IC among patients enrolled in the study.
309 studies on the registry are indexed under Intermittent Claudication; 46 are open to participants now.
This study's planned enrollment of 200 is above the median of 74 across 242 interventional studies indexed under Intermittent Claudication.
Browse Intermittent Claudication studies →VA Office of Research and Development is the lead sponsor of 1,771 studies on the registry; 392 are open to participants now.
Of its 213 completed or terminated interventional studies of FDA-regulated products, 185 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Medically stable, optimal medical therapy (for >3 months prior to randomization which includes - statin and anti- therapy, blood pressure control, smoking cessation and physical activity counseling)
a. Participants may not comply with the above measures to meet inclusion criteria, but investigator driven attempts to maximize the optimal medical therapy, as tolerated, for each participant prior to trial enrollment
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
daily by mouth
Drug: Metformin ER
daily by mouth
Drug: placebo
Oral medication typically used for Type 2 diabetes with presumed anti-inflammatory properties
Also known as: Glucophage
Matched to active study drug
Maximal Walking distance on the 6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity
Time frame: 6 month
6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
Time frame: 6 month
6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
Time frame: 12 month
Cardiopulmonary exercise test
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
Time frame: 6 month
Cardiopulmonary exercise test
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
Time frame: 12 month
EndoPAT
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Time frame: 6 month
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
Time frame: 6 month
EndoPAT
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Time frame: 12 month
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
Time frame: 12 month
Ankle brachial index and pulse volume recording
The ABI and PVR assess regional lower extremity blood supply in large-vessels and contribution of collaterals
Time frame: 6 month
Ankle brachial index
The ABI assesses regional lower extremity blood supply in large-vessels and contribution of collaterals
Time frame: 12 month
Health related quality of life questionnaire
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire \[VascQol6\]) health related quality of life questionnaires.
Time frame: 6 month
Health related quality of life questionnaires
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire \[VascQol6\]) health related quality of life questionnaires.
Time frame: 12 month
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Time frame: 6 month
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Time frame: 12 month
Freedom from major cardiac and major limb events
Major cardiac events include: composite of CVD mortality, myocardial ischemia, coronary revascularization, hospitalization for heart failure, non-fatal stroke, and transient ischemic attack. Major adverse limb events include: composite of minor and major amputations, revascularization
Time frame: 12 month
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Metformin
VA Office of Research and Development →