- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01901224
Metformin, Muscle Energetics, and Vascular Function in Older Adults With Peripheral Artery Disease
The investigators are doing this research study to find out if taking Metformin improves walking ability in patients with peripheral arterial disease (PAD). In PAD the arteries (blood vessels) in the legs are narrowed because of the build up of plaque. The leg muscle can hurt in patients with PAD and this is usually described as a cramp or tiredness. This pain is called intermittent claudication. Metformin is an FDA approved medication for the treatment of diabetes. The investigators believe that Metformin may help your leg muscles work better.
The investigators will enroll up to 100 subjects in order to find 60 subjects with PAD at Brigham and Women's Hospital (BWH).
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 40 years or greater
- Intermittent claudication for 6 months or greater
- Maximal walk time between 1-20 minutes on all ETTs
- Resting ABI ≤ 0.9 in index leg at baseline
- ABI falls ≥ 20% in index leg 1 minute post baseline ETT
- MWT variability < 20%
Exclusion Criteria:
- Type 1 or Type 2 Diabetes
- Limb-threatening ischemia (rest pain, ulceration, gangrene)
- Peripheral vascular surgery or PCI within 6 months
- MI or CABG within 6 months
- Carotid endarterectomy (CEA) within 6 months
- Cerebrovascular accident or TIA within 6 months
- Uncontrolled hypertension (SBP > 140 mmHg, DBP >90 mmHg)
- Pentoxifylline/Cilostazol added/changed within 3 months
- HMG-CoA reductase inhibitor added/changed within 3 months
- Exercise limitations other than claudication (heart failure, angina, COPD, arthritis, neuropathy, etc.)
- Serum creatinine ≥ 1.5 mg/dL
- Pregnant or plans to become pregnant
- 2 hour Oral Glucose Tolerance Test (OGTT) > 200 mg/dL
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Metformin 1000 mg
metformin 1000 mg twice daily: In order to avoid gastrointestinal side effects, the starting dose of metformin will be 500 mg twice daily.
After one week, the dose will be increased to 1000 mg twice daily (as two 500 mg tablets twice daily).
Subjects will be instructed to take medications with breakfast and with dinner.
|
|
PLACEBO_COMPARATOR: Control
placebo twice daily: In order to maintain blinding during the titration period, individuals randomized to placebo will receive one placebo tablet twice daily for one week, followed by an increase to 2 placebo tablets twice daily.
Subjects will be instructed to take medications with breakfast and with dinner.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in PCr Recovery Time
Time Frame: baseline, 12 weeks
|
PCr recovery time, measured in seconds, is a measure of skeletal muscle metabolic function.
PCr is a transport molecule and reservoir of high-energy phosphate bonds, which is important for cellular energetics.
Phosphocreatine regeneration depends upon the skeletal muscle mitochondrial cells capacity for oxidative phosphorylation.
We will measure PCr recovery time at baseline and after 12 weeks of treatment with metformin or placebo as an in vivo measure of mitochondrial function.
Higher Pcr relative to P(i) during recovery is better and shorter recovery times are better.
|
baseline, 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Flow-mediated Dilation (FMD)
Time Frame: baseline, 12 weeks
|
Flow mediated vasodilation of the brachial artery is a measure of endothelium-dependent vasodilation.
Higher flow-mediated dilation (FMD), measured as the diameter of the brachial artery in millimeters, and reported as percent change after a flow stimulus compered to basal measurement, is better, indicative of better endothelial function.
|
baseline, 12 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Maximal Treadmill Walking Time
Time Frame: baseline, 12 weeks
|
Maximal treadmill walking time is measured in minutes or seconds.
Higher values indicate a better outcome.
|
baseline, 12 weeks
|
Change in Pain-free Treadmill Walking Time
Time Frame: baseline, 12 weeks
|
Pain-free treadmill walking time is measured in minutes or seconds.
Higher values indicate a better outcome.
|
baseline, 12 weeks
|
Change in Oxygen Consumption
Time Frame: baseline, 12 weeks
|
Oxygen consumption is measured in ml/kg/min.
Higher values indicate better outcomes.
|
baseline, 12 weeks
|
Change in Six Minute Walk Test
Time Frame: baseline, 12 weeks
|
The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.The 6 MWT is measured in meters, and higher values indicate better outcomes.
|
baseline, 12 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2013P001042
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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