None listed
Conditions
Brief summary
This parallel group, blinded, placebo-controlled randomised trial will determine whether 1500mg/day of metformin administered for 6 months improves walking ability in PAD patients. Based on sample size calculations focused on the minimal clinically important difference, 250 PAD patients that do not have diabetes, renal or cardiac failure will be included. The trial will employ an independently run minimisation randomisation system and identical appearance, weight and packaging of drug and placebo to ensure blinding of investigations, patients and assessors, along with balancing of important determinants of outcome. The primary outcome measure will be the 6-month maximum walking distance during a six minute walk test. Secondary outcomes will include physical activity assessed over 7 days with an accelerometer, health-related quality of life, leg blood supply assessed with ankle-brachial pressure index and circulating concentrations of key markers of angiogenesis. Adverse events will be monitored by an independent data monitoring committee. Previous trials indicate metformin is safe for patients without diabetes.
Interventions
Study Design: Parallel group, blinded, placebo-controlled randomised clinical trial.
Intervention - metformin: up to one 500mg capsule three times per day (1500mg/day).
Titration (1-6 weeks): Participants in both arms will have their medications up titrated over 6 weeks to tolerance based on symptoms.
Week 1 & 2: one 500mg capsule once per day with food (~500mg/day).
Week 3 & 4: one 500mg capsule twice per day with food (~1000mg/day).
Week 5 & 6: one 500mg capsule three times per day with fo
Study Design: Parallel group, blinded, placebo-controlled randomised clinical trial. Intervention - metformin: up to one 500mg capsule three times per day (1500mg/day). Titration (1-6 weeks): Participants in both arms will have their medications up titrated over 6 weeks to tolerance based on symptoms. Week 1 & 2: one 500mg capsule once per day with food (~500mg/day). Week 3 & 4: one 500mg capsule twice per day with food (~1000mg/day). Week 5 & 6: one 500mg capsule three times per day with food (~1500mg/day). Follow-up (24 weeks post titration period): participants will continue to take the maximum tolerated dose of drug up to 1500mg/day for 24 weeks. Week 7-30: one 500mg capsule three times per day with food (~1500mg/day). Participants will be given a calendar diary to keep track of the dose to be taken each week and to record the number and time of day the capsules are taken. The purpose of the diary is to assist the participant in taking the right amount of drug at the right time and day. Participants will be asked to return any empty bottles and remaining capsules to the study coordinator for a pill count in order to assess adherence.
Sponsors
James Cook University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. PAD diagnosed by a vascular specialist based on current guidelines including PAD symptoms and absence of lower limb pulses or resting ABPI <0.9 or >1.4, or imaging evidence of lower limb arterial stenosis or occlusion; 2. Able to walk independently, with or without walking aids, but walking limited by intermittent claudication based on history and assessment by experienced observer during a six minute walk test; 3. No currently planned peripheral vascular intervention; 4. No contraindications to metformin, including renal impairment (defined as estimated glomerular filtration rate <45ml/min/1.73m2) and severe heart failure requiring in-patient treatment within the last 12 months or leading to shortness of breath at rest.
Exclusion criteria
1. Asymptomatic PAD; 2. Patients currently involved in an exercise program for treating PAD; 3. Patients with severe PAD, such as rest pain or gangrene requiring urgent vascular intervention; 4. Previous major lower limb amputation; 5. Diabetes defined by Haemoglobin A1C (HbA1c) equal or greater than 6.5%. 6. Terminal illness making it unlikely the patient will survive 6 months; 7. Involvement in any other drug trial; 8. Clinical concern from the treating physician that the patient is not suitable for the trial.
Outcome results
None listed