Evidence map›Paper›PMID 36681798›Full record

ArticleBMC cardiovascular disorders2023

MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol.

Katherine M Reitz, Andrew D Althouse, Daniel E Forman, Brian S Zuckerbraun, Yoram Vodovotz, Ruben Zamora, Robert L Raffai, Daniel E Hall, Edith Tzeng

Registry-linked trialOpen access · goldFull text readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cardiovascular disorders, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05132439 (Metformin BenefIts Lower Extremities With Intermittent Claudication), which is not on this map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05132439 phase3recruitingnot on this map

Metformin BenefIts Lower Extremities With Intermittent Claudication (MOBILE_IC)

TypeinterventionalSponsorVA Office of Research and DevelopmentRan2022 to 2032Enrolled200ConditionsIntermittent ClaudicationArmsMetformin ER, placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Katherine M ReitzDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Andrew D AlthouseSchool of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Daniel E FormanDepartment of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Brian S ZuckerbraunDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Yoram VodovotzDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Ruben ZamoraDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Robert L RaffaiVA Medical Center, San Francisco, CA, USA.
Daniel E HallDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
Edith TzengDepartment of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, Pittsburgh, PA, 15213, USA. tzenge@upmc.edu.ORCID 0000-0002-5762-6798
University of Pittsburgh · USSan Francisco VA Medical Center · US

Funding

Vascular Surgery Research Training (VascTrain) ProgramT32HL098036 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Edith Tzeng · 2010 to 2026
$7.2M
Metformin BenefIts Lower Extremities with Intermittent Claudication (MOBILE_IC)I01CX002150 · VA · VETERANS HEALTH ADMINISTRATION · PI TZENG, EDITH · 2021 to 2025
–
CSRD VA I01 CX002150NHLBI NIH HHS T32 HL098036NIA NIH HHS L30 AG064730
6 · The paper itself

Abstract

backgroundPeripheral artery disease (PAD) affects over 230 million people worldwide and is due to systemic atherosclerosis with etiology linked to chronic inflammation, hypertension, and smoking status. PAD is associated with walking impairment and mobility loss as well as a high prevalence of coronary and cerebrovascular disease. Intermittent claudication (IC) is the classic presenting symptom for PAD, although many patients are asymptomatic or have atypical presentations. Few effective medical therapies are available, while surgical and exercise therapies lack durability. Metformin, the most frequently prescribed oral medication for Type 2 diabetes, has salient anti-inflammatory and promitochondrial properties. We hypothesize that metformin will improve function, retard the progression of PAD, and improve systemic inflammation and mitochondrial function in non-diabetic patients with IC.

methods200 non-diabetic Veterans with IC will be randomized 1:1 to 180-day treatment with metformin extended release (1000 mg/day) or placebo to evaluate the effect of metformin on functional status, PAD progression, cardiovascular disease events, and systemic inflammation. The primary outcome is 180-day maximum walking distance on the 6-min walk test (6MWT). Secondary outcomes include additional assessments of functional status (cardiopulmonary exercise testing, grip strength, Walking Impairment Questionnaires), health related quality of life (SF-36, VascuQoL), macro- and micro-vascular assessment of lower extremity blood flow (ankle brachial indices, pulse volume recording, EndoPAT), cardiovascular events (amputations, interventions, major adverse cardiac events, all-cause mortality), and measures of systemic inflammation. All outcomes will be assessed at baseline, 90 and 180 days of study drug exposure, and 180 days following cessation of study drug. We will evaluate the primary outcome with linear mixed-effects model analysis with covariate adjustment for baseline 6MWT, age, baseline ankle brachial indices, and smoking status following an intention to treat protocol. DISCUSSION: MOBILE IC is uniquely suited to evaluate the use of metformin to improve both systematic inflammatory responses, cellular energetics, and functional outcomes in patients with PAD and IC.

trial registrationThe prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

Indexed as

Diabetes Mellitus, Type 2MetforminPeripheral Arterial DiseaseHumansIntermittent ClaudicationLower ExtremityProspective StudiesQuality of LifeRandomized Controlled Trials as TopicMetforminAnti-inflammatory agentsAtherosclerosisClinical trial protocolIntermittent claudicationMetforminPeripheral artery disease

Identifiers

PMID36681798
PMCPMC9862509
OpenAlexW4317605725

What OpenQuestion holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.