Clinical Trial: The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of Metformin for the Assessment of Changes in Functional Capacity, Endothelial Function, and Hemodynamics in Individuals With Periphe
Brief Summary: The purpose of this study is to determine the effects of metformin on functional capacity (pain-free and maximum walking times) in individuals with peripheral artery disease (PAD)-related intermittent claudication.
Detailed Summary:
Background and Rationale:
Metformin has demonstrable efficacy in slowing or reversing the progression of various insulin-resistant disease states - most notably type 2 diabetes and pre-diabetes. In seeking to establish proof-of-concept that insulin resistance is a suitable pathophysiological target in the treatment of PAD-related intermittent claudication (pain in the leg muscles during walking, which resolves on exercise cessation), this study will determine whether the known insulin-sensitizing effects of metformin translate to alleviation of the functional limitations imposed by claudication.
Study Design:
A total of 80 individuals with PAD-related intermittent claudication will be randomised (1:1) to either metformin or matching placebo for 16-18 weeks (double-blind, parallel group design). The maximum daily dose of metformin will be 2000mg (up-titrated from half this dose at 2 weeks if tolerated).
Primary Hypothesis:
Improvement in functional capacity follows metformin therapy in individuals with PAD-related intermittent claudication. Change in functional capacity will be assessed by the co-primary endpoints of pain-free and maximum walking times during a standard graded treadmill exercise test.
Secondary Aims:
Exercise testing for functional performance will be complemented by assessments of perceived physical functioning / quality of life in the daily life setting (using standard questionnaires). As previous studies have indicated cardiovascular effects of metformin incremental to blood glucose-lowering, this study will also investigate potential mechanisms of efficacy r
Sponsor: Baker IDI Heart and Diabetes Institute
Current Primary Outcome:
- Change in pain-free walking time [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]Pain-free walking time (time to onset of claudication) will be measured during a graded treadmill exercise test.
- Change in maximum walking time [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]Maximum walking time will be measured during a graded treadmill exercise test.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Change in questionnaire-based markers of quality of life / perceived functional capacity [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
- Change in endothelial function [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
- Change in skeletal muscle blood flow response to insulin [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
- Change in skeletal muscle blood flow response to acute exercise [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
- Change in insulin sensitivity [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
- Change in objectively measured physical activity / sedentary behaviour in the daily life setting. [ Time Frame: Measured at baseline and following 16-18 weeks treatment ]
Original Secondary Outcome: Same as current
Information By: Baker IDI Heart and Diabetes Institute
Dates:
Date Received: February 22, 2013
Date Started: July 2013
Date Completion:
Last Updated: February 7, 2016
Last Verified: February 2016