The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication

NCT01799057 | Terminated Phase 4

• 1 other identifier: 493/12
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Keywords

Peripheral Arterial Disease; Intermittent Claudication; Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Atherosclerosis; Insulin Resistance; Glucose Metabolism; Blood Glucose; Metformin; Biguanides; Hypoglycemic Agents; Endothelium, Vascular; Hemorheology; Blood Circulation; Regional Blood Flow; Microcirculation; Exercise; Physical Fitness; Exercise Test; Sedentary Lifestyle; Quality of Life; Plethysmography

Outcome Measures

Primary Outcomes (2)

• Change in pain-free walking time

  Pain-free walking time (time to onset of claudication) will be measured during a graded treadmill exercise test.

  Measured at baseline and following 16-18 weeks treatment

• Change in maximum walking time

  Maximum walking time will be measured during a graded treadmill exercise test.

  Measured at baseline and following 16-18 weeks treatment

Secondary Outcomes (6)

• Change in questionnaire-based markers of quality of life / perceived functional capacity

  Measured at baseline and following 16-18 weeks treatment

• Change in endothelial function

  Measured at baseline and following 16-18 weeks treatment

• Change in skeletal muscle blood flow response to insulin

  Measured at baseline and following 16-18 weeks treatment

• Change in skeletal muscle blood flow response to acute exercise

  Measured at baseline and following 16-18 weeks treatment

• Change in insulin sensitivity

  Measured at baseline and following 16-18 weeks treatment

Other Outcomes (3)

• Change in glucose uptake and insulin signalling mechanisms in skeletal muscle (exploratory endpoint)

  Measured at baseline and following 16-18 weeks treatment

• Change in skeletal muscle oxidative capacity and substrate utilization (exploratory endpoint)

  Measured at baseline and following 16-18 weeks treatment

• Change in inflammation, fibrinolysis and coagulation (exploratory endpoint)

  Measured at baseline and following 16-18 weeks treatment

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin at a maximum dose of 1000mg twice daily for 16-18 weeks (i.e. maximum of 2000mg per day).

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Matching placebo twice daily for 16-18 weeks.

Drug: Placebo

Interventions

Metformin DRUG

Participants 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.

Also known as: Diaformin

Metformin

Placebo DRUG

Participants randomized to placebo will take matching oral capsules according to the same dose schedule specified for the metformin intervention.

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Baker Heart and Diabetes Institute: lead

Study Sites (1)

Baker IDI Heart and Diabetes Institute

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication; Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Atherosclerosis; Insulin Resistance; Motor Activity; Sedentary Behavior

Interventions

Metformin

Condition Hierarchy (Ancestors)

Arteriosclerosis; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Bronwyn A Kingwell, PhD

  Baker Heart and Diabetes Institute

  PRINCIPAL INVESTIGATOR

• Stephen J Duffy, MD, PhD

  Baker Heart and Diabetes Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2013
• First Posted: February 26, 2013
• Study Start: July 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 9, 2016

Record last verified: 2016-02

Locations

AU (1)