Intermittent ClaudicationPhase 3MOBILE ICNCT05132439
MetfOrmin BenefIts Lower Extremities With Intermittent Claudication
A Phase 3 study testing Metformin ER in people with Intermittent Claudication, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 35 to 89 years
- Conditions the study is for
- Intermittent Claudication
- What is being tested?
- Metformin ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2022to 28 Feb 2032
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 35 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and Female Veteran >35 \& <89
- Symptoms of Intermittent claudication
- Medically stable, optimal medical therapy (for >3 months prior to randomization which includes - statin and anti-platelet therapy, blood pressure control, smoking cessation and physical activity counseling)
- 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
- PAD as defined by ABI <0.9 or >0.9 with evidence of PAD as documented by pulse volume recordings (within 6 months prior to expected randomization date)
- Maximum Walking Distance (MWD) on the 6-minute walk test (6MWT) of greater than or equal to 50 meters with onset of pain before or at 400 meters without the use of a walker (cane is acceptable; within 6 months of expected randomization date)
Who cannot join
- Diabetes (Type I or II) or Hemoglobin A1c>6.5 (within 6 months of expected randomization)
- Currently Taking metformin or have previously taken metformin (within 6 months of enrollment)
- Medical condition that limit their ability to ambulate other than PAD (i.e., Angina, CHF, pulmonary disease requiring oxygen, malignancy requiring treatment, etc.)
- Prior above or below knee amputation
- Critical limb threatening ischemia (i.e., non-healing wounds or rest pain)
- Planned hospital admission, major operation, or lower extremity revascularization to be completed (within 12 months after expected randomization date)
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- Prior major operation or lower extremity revascularization (within the 3 months before expected randomization)
- Unable to complete quality of life testing due to Non-English Speaking and/or Dementia
- Kidney disease - dialysis or eGFR<45 (within 6 months of expected randomization date)*
- Planned iodinated contrasted study (within 6 months of expected randomization date)
- Evidence current or history of hepatic failure
- Women who are pregnant or breast feeding
- Unable to swallow uncrushed pills
- Investigator expects inclusion could cause harm to subject
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240
Susan L Barr, 412-360-2387, susan.barr2@va.gov
Samantha A Bonant, BS, (412) 360-3788, samantha.bonant@va.gov
About this study
Official title: Metformin BenefIts Lower Extremities With Intermittent Claudication (MOBILE_IC)
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.
Read the detailed description
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.
- Conditions
- Intermittent Claudication
- Being tested
- Metformin ER, placebo
- Keywords
- Peripheral artery disease, intermittent claudication, metformin, anti-inflammatory agents, clinical trial protocol, atherosclerosis
- Medical subject headings
- Intermittent Claudication, Peripheral Arterial Disease, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin ERDrug
Also called Glucophage
Oral medication typically used for Type 2 diabetes with presumed anti-inflammatory properties
placeboDrug
Matched to active study drug
| Study group | Role | What they receive |
|---|---|---|
| Metformin ER 1000mg | Experimental | daily by mouth Receives: Drug: Metformin ER |
| Matching placebo | Placebo comparator | daily by mouth Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 month
Secondary outcomes (15)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 6 month
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
Measured: 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
Measured: 12 month
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
Measured: 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
Measured: 6 month
Ankle brachial index
The ABI assesses regional lower extremity blood supply in large-vessels and contribution of collaterals
Measured: 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.
Measured: 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.
Measured: 12 month
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Measured: 6 month
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Measured: 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
Measured: 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2021
- Study start1 Mar 2022
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intermittent ClaudicationStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- Two arm randomization to 1000mg metformin ER or placebo daily with 1:1 parallel randomization, Randomization stratification will be based on baseline Maximum Walking Distance on the 6 Minute Walk Test and smoking status
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Pittsburgh, Northwestern University, San Francisco Veterans Affairs Medical Center
- Responsible party
- Sponsor
- Investigators
- Edith I. Tzeng, MD, Principal investigator, VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05132439
- Sponsor's protocol ID
- CARB-012-20F
- Other IDs
- I01CX002150
- Acronym
- MOBILE IC
- Status last verified
- Apr 2026
- First submitted
- 12 Nov 2021
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Reitz KM, Althouse AD, Forman DE, Zuckerbraun BS, Vodovotz Y, Zamora R, Raffai RL, Hall DE, Tzeng E. MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol. BMC Cardiovasc Disord. 2023 Jan 21;23(1):38. doi: 10.1186/s12872-023-03047-8.
PubMed 36681798
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin BenefIts Lower Extremities With Intermittent Claudication (MOBILE_IC)
- ClinicalTrials.gov ID
- NCT05132439
- Acronym / sponsor ID
- MOBILE IC / CARB-012-20F
- Conditions
- Intermittent Claudication
- Keywords
- Peripheral artery disease, intermittent claudication, metformin, anti-inflammatory agents, clinical trial protocol, atherosclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Pittsburgh, Northwestern University, San Francisco Veterans Affairs Medical Center
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2032 (estimated)
- First posted
- 24 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two arm randomization to 1000mg metformin ER or placebo daily with 1:1 parallel randomization, Randomization stratification will be based on baseline Maximum Walking Distance on the 6 Minute Walk Test and smoking status
| Arm | Type | Receives |
|---|---|---|
| Metformin ER 1000mg | Experimental | Drug: Metformin ERdaily by mouth |
| Matching placebo | Placebo comparator | Drug: placebodaily by mouth |
Who may qualify
- Ages
- 35 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and Female Veteran >35 \& <89
- Symptoms of Intermittent claudication
- Medically stable, optimal medical therapy (for >3 months prior to randomization which includes - statin and anti-platelet therapy, blood pressure control, smoking cessation and physical activity counseling)
- PAD as defined by ABI <0.9 or >0.9 with evidence of PAD as documented by pulse volume recordings (within 6 months prior to expected randomization date)
- Maximum Walking Distance (MWD) on the 6-minute walk test (6MWT) of greater than or equal to 50 meters with onset of pain before or at 400 meters without the use of a walker (cane is acceptable; within 6 months of expected randomization date)
Key exclusion criteria (14 listed)
- Diabetes (Type I or II) or Hemoglobin A1c>6.5 (within 6 months of expected randomization)
- Currently Taking metformin or have previously taken metformin (within 6 months of enrollment)
- Medical condition that limit their ability to ambulate other than PAD (i.e., Angina, CHF, pulmonary disease requiring oxygen, malignancy requiring treatment, etc.)
- Prior above or below knee amputation
- Critical limb threatening ischemia (i.e., non-healing wounds or rest pain)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin ERAlso: GlucophageOral medication typically used for Type 2 diabetes with presumed anti-inflammatory properties | Drug | Metformin ER 1000mg |
| placeboMatched to active study drug | Drug | Matching placebo |
Primary outcome
Maximal Walking distance on the 6 minute walk test
Time frame: 6 month
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity
15 secondary outcomes
6 minute walk test
Time frame: 6 month
6 minute walk test
Time frame: 12 month
Cardiopulmonary exercise test
Time frame: 6 month
Cardiopulmonary exercise test
Time frame: 12 month
EndoPAT
Time frame: 6 month
Grip Strength
Time frame: 6 month
EndoPAT
Time frame: 12 month
Grip Strength
Time frame: 12 month
Ankle brachial index and pulse volume recording
Time frame: 6 month
Ankle brachial index
Time frame: 12 month
Health related quality of life questionnaire
Time frame: 6 month
Health related quality of life questionnaires
Time frame: 12 month
Walking Impairment Questionnaire
Time frame: 6 month
Walking Impairment Questionnaire
Time frame: 12 month
Freedom from major cardiac and major limb events
Time frame: 12 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Derived from this study: PubMed 36681798Reitz KM, Althouse AD, Forman DE, Zuckerbraun BS, Vodovotz Y, Zamora R, Raffai RL, Hall DE, Tzeng E. MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol. BMC Cardiovasc Disord. 2023 Jan 21;23(1):38. doi: 10.1186/s12872-023-03047-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Edith I. Tzeng, MD principal investigator
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin ER in people with Intermittent Claudication, run by VA Office of Research and Development at 1 site 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 6 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Edith I Tzeng, MD ((412) 360-1657, Edith.Tzeng@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Walking distance on the 6 minute walk test (time frame: 6 month). 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 NCT05132439, which also lists 1 linked publication.
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 21 Apr 2026.