Peripheral Arterial Disease | The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Peripheral Arterial Disease research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: - Age ≥40 years old. - Resting ankle-brachial index (ABI) ≤0.90 in the limiting leg(s), or a >20% reduction in the ABI measured immediately post-exercise where the resting ABI is >0.90. In cases of incompressible arteries in the limiting leg(s) (i.e. ABI ≥1.40), a toe-brachial index (TBI) of ≤0.70 is required. - Peripheral artery stenosis/occlusion in the limiting leg(s), documented by duplex ultrasonography or other imaging tests. - Stable (i.e. 3-month history) intermittent claudication in at least one PAD-affected leg. - Maximum walking time during graded treadmill exercise testing (Gardner-Skinner protocol) ≥1 minute and ≤16 minutes. - Concurrent medications that may affect primary, secondary or exploratory endpoints have remained stable over the previous 3 months. - Have given signed informed consent to participate in the study. Exclusion Criteria: - Identification of any other medical condition requiring immediate therapeutic intervention. - Clinically significant abnormal electrocardiogram (ECG) at rest or during exercise that represents a contraindication to study procedures or the study drug. - Myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft surgery (CABG), or other major surgery within the previous 6 months. - Exercise capacity limited by a factor other than PAD-related intermittent claudication. - Any condition that precludes valid completion of a treadmill exercise test. - Critical limb ischemia in either leg, defined as PAD-related chronic ischemic rest pain or skin lesions (ulcers, gangrene). - Previous peripheral revascularisation or other surgical treatment for PAD in the previous 6 months. - Known non-atherosclerotic cause of PAD. - Active cancer. - Uncontrolled hypertension (resting brachial blood pressure ≥160/100 mmHg). - Evidence of pharmacologically-treated or poorly controlled (i.e. HbA1c ≥7.5%) type 2 diabetes or other class of diabetes (e.g. type 1 diabetes). - Known intolerance or contraindication(s) to metformin. - Known contraindication(s) to \"Definity\" (perflutren lipid microsphere). - Participation or intention to participate in another clinical research study during the study period. - History of non-compliance to medical regimens or unwillingness to comply with the study protocol. - Any other condition that in the opinion of the Investigators would confound the evaluation and interpretation of the data. - Persons directly involved in the execution of the protocol. - Incapable of providing written informed consent due to cognitive, language, or other reasons.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Peripheral Arterial Disease
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:MetforminParticipants randomized to metformin will be treated at a maximum dose of 2000mg per day (i.e. 1000mg twice daily for 16-18 weeks; up-titrated from 500mg twice daily for the first 2 weeks). Participants may complete the 16-18 week treatment intervention at the lower dose of 500mg twice daily if limited by side effects.
Drug:PlaceboParticipants randomized to placebo will take matching oral capsules according to the same dose schedule specified for the metformin intervention.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
MetforminMetformin at a maximum dose of 1000mg twice daily for 16-18 weeks (i.e. maximum of 2000mg per day).
PlaceboMatching placebo twice daily for 16-18 weeks.
Start Date: July 2013
Completed Date: December 2014
Phase: Phase 4
Primary Outcome: Change in pain-free walking time
Secondary Outcome: Change in questionnaire-based markers of quality of life / perceived functional capacity
Study sponsors, principal investigator, and references
Principal Investigator: Bronwyn A Kingwell, PhD
Lead Sponsor: Baker IDI Heart and Diabetes Institute