MetfOrmin BenefIts Lower Extremities With Intermittent Claudication

NCT05132439 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CARB-012-20FI01CX002150
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Intermittent Claudication

Keywords

Peripheral artery disease; intermittent claudication; metformin; anti-inflammatory agents; clinical trial protocol; atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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

  6 month

Secondary Outcomes (15)

• 6 minute walk test

  6 month

• 6 minute walk test

  12 month

• Cardiopulmonary exercise test

  6 month

• Cardiopulmonary exercise test

  12 month

• EndoPAT

  6 month

Study Arms (2)

Metformin ER 1000mg

EXPERIMENTAL

daily by mouth

Drug: Metformin ER

Matching placebo

PLACEBO COMPARATOR

daily by mouth

Drug: placebo

Interventions

Metformin ER DRUG

Oral medication typically used for Type 2 diabetes with presumed anti-inflammatory properties

Also known as: Glucophage

Metformin ER 1000mg

placebo DRUG

Matched to active study drug

Matching placebo

Eligibility Criteria

• Age: 35 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Pittsburgh: collaborator
• Northwestern University: collaborator
• San Francisco Veterans Affairs Medical Center: collaborator

Study Sites (1)

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 36681798 DERIVED

MeSH Terms

Conditions

Intermittent Claudication; Peripheral Arterial Disease; Atherosclerosis

Interventions

Metformin

Condition Hierarchy (Ancestors)

Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Edith I. Tzeng, MD

  VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edith I Tzeng, MD

CONTACT

(412) 360-1657; Edith.Tzeng@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a triple-blinded randomized controlled trial. Therefore, the allocation of participants to either placebo or metformin is unknown by the participant, research personnel, and investigator. The study statistician will not be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 12, 2021
• First Posted: November 24, 2021
• Study Start: March 1, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2032
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)