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

BMC Cardiovascular Disorders

Study Protocol

Daniel E. Forman¹  Ruben Zamora²  Yoram Vodovotz³  Brian S. Zuckerbraun⁴  Daniel E. Hall⁵  Katherine M. Reitz⁶  Edith Tzeng⁷  Andrew D. Althouse⁸  Robert L. Raffai⁹ 

[1] Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;Geriatrics Research, Education, and Clinical Care, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Center for Inflammation and Regeneration Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA;Center for Systems Immunology, University of Pittsburgh, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Department of Surgery, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Department of Surgery, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;Geriatrics Research, Education, and Clinical Care, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;Wolff Center, UPMC, Pittsburgh, PA, USA;Center for Health Equity Research and Promotion, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Division of Vascular Surgery, University of Pittsburgh, Pittsburgh, PA, USA;Department of Surgery, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;Department of Surgery, University of Pittsburgh, South Tower, Rm 351.6, 200 Lothrop Street, 15213, Pittsburgh, PA, USA;Division of Vascular Surgery, University of Pittsburgh, Pittsburgh, PA, USA;Department of Surgery, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA;School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;VA Medical Center, San Francisco, CA, USA;

关键词: Peripheral artery disease;    Intermittent claudication;    Metformin;    Anti-inflammatory agents;    Clinical trial protocol;    Atherosclerosis;   

DOI  :  10.1186/s12872-023-03047-8

 received in 2022-09-23, accepted in 2023-01-05,  发布年份 2023

来源: Springer

【 摘 要 】

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.DiscussionMOBILE 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 Registration: The prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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