Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2025-12-29 @ 4:57 AM
Study NCT ID:
NCT01799057
Status:
TERMINATED
Last Update Posted:
2016-02-09
First Post:
2013-02-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Sponsor:
Baker Heart and Diabetes Institute
Organization:
Study Overview
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 Peripheral Artery Disease-Related Intermittent Claudication
Status:
TERMINATED
Status Verified Date:
2016-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The trial has been terminated due to difficulties with recruitment.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
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 relating to the primary endpoints, including changes in endothelial function, blood flow responses to various stimuli (including insulin and acute exercise), insulin sensitivity, and physical activity / sedentary behaviours. Changes in relevant clinical data (including ankle-brachial index and limb hemodynamics by duplex scanning) will also be determined.
Outcomes and Significance:
The unmet clinical need of efficacious medical therapies for intermittent claudication is a growing problem given the increasing prevalence of PAD worldwide. If positive, this study will identify a new potential treatment that is already widely available. The study will also inform on novel mechanistic targets with relevance to existing and future therapeutic strategies.
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 relating to the primary endpoints, including changes in endothelial function, blood flow responses to various stimuli (including insulin and acute exercise), insulin sensitivity, and physical activity / sedentary behaviours. Changes in relevant clinical data (including ankle-brachial index and limb hemodynamics by duplex scanning) will also be determined.
Outcomes and Significance:
The unmet clinical need of efficacious medical therapies for intermittent claudication is a growing problem given the increasing prevalence of PAD worldwide. If positive, this study will identify a new potential treatment that is already widely available. The study will also inform on novel mechanistic targets with relevance to existing and future therapeutic strategies.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: