Back to resultsMetfOrmin BenefIts Lower Extremities With Intermittent Claudication (MOBILE IC)
Primary Purpose
Intermittent Claudication
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metformin ER
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Intermittent Claudication focused on measuring Peripheral artery disease, intermittent claudication, metformin, anti-inflammatory agents, clinical trial protocol, atherosclerosis
Eligibility Criteria
Inclusion Criteria:
- Male and Female Veteran >35 & <89
- Symptoms of Intermittent claudication
Medically stable, optimal medical therapy (for >3 months prior to randomization which includes - statin and anti-platelet therapy, blood pressure control, smoking cessation and physical activity counseling)
a. Participants may not comply with the above measures to meet inclusion criteria, but investigator driven attempts to maximize the optimal medical therapy, as tolerated, for each participant prior to trial enrollment
- PAD as defined by ABI <0.9 or >0.9 with evidence of PAD as documented by pulse volume recordings (within 6 months prior to expected randomization date)
- Maximum Walking Distance (MWD) on the 6-minute walk test (6MWT) of greater than or equal to 50 meters with onset of pain before or at 400 meters without the use of a walker (cane is acceptable; within 6 months of expected randomization date)
Exclusion Criteria:
- Diabetes (Type I or II) or Hemoglobin A1c>6.5 (within 6 months of expected randomization)
- Currently Taking metformin or have previously taken metformin (within 6 months of enrollment)
- Medical condition that limit their ability to ambulate other than PAD (i.e., Angina, CHF, pulmonary disease requiring oxygen, malignancy requiring treatment, etc.)
- Prior above or below knee amputation
- Critical limb threatening ischemia (i.e., non-healing wounds or rest pain)
- Planned hospital admission, major operation, or lower extremity revascularization to be completed (within 12 months after expected randomization date)
- Prior major operation or lower extremity revascularization (within the 3 months before expected randomization)
- Unable to complete quality of life testing due to Non-English Speaking and/or Dementia
- Kidney disease - dialysis or eGFR<45 (within 6 months of expected randomization date)*
- Planned iodinated contrasted study (within 6 months of expected randomization date)
- Evidence current or history of hepatic failure
- Women who are pregnant or breast feeding
- Unable to swallow uncrushed pills
- Investigator expects inclusion could cause harm to subject
Sites / Locations
- VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PARecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin ER 1000mg
Matching placebo
Arm Description
daily by mouth
daily by mouth
Outcomes
Primary Outcome Measures
Maximal Walking distance on the 6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity
Secondary Outcome Measures
6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
6 minute walk test
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
Cardiopulmonary exercise test
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
Cardiopulmonary exercise test
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
EndoPAT
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
EndoPAT
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Grip Strength
Grip strength with a dynamometer provides a digital reading of force
Ankle brachial index and pulse volume recording
The ABI and PVR assess regional lower extremity blood supply in large-vessels and contribution of collaterals
Ankle brachial index
The ABI assesses regional lower extremity blood supply in large-vessels and contribution of collaterals
Health related quality of life questionnaire
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire [VascQol6]) health related quality of life questionnaires.
Health related quality of life questionnaires
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire [VascQol6]) health related quality of life questionnaires.
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Walking Impairment Questionnaire
A subjective measure of patient-reported walking performance developed for PAD
Freedom from major cardiac and major limb events
Major cardiac events include: composite of CVD mortality, myocardial ischemia, coronary revascularization, hospitalization for heart failure, non-fatal stroke, and transient ischemic attack. Major adverse limb events include: composite of minor and major amputations, revascularization
Full Information
NCT ID
NCT05132439
First Posted
November 12, 2021
Last Updated
October 16, 2023
Sponsor
VA Office of Research and Development
Collaborators
University of Pittsburgh, Northwestern University, San Francisco Veterans Affairs Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT05132439
Brief Title
MetfOrmin BenefIts Lower Extremities With Intermittent Claudication
Acronym
MOBILE IC
Official Title
Metformin BenefIts Lower Extremities With Intermittent Claudication (MOBILE_IC)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
February 28, 2026 (Anticipated)
Study Completion Date
February 28, 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
University of Pittsburgh, Northwestern University, San Francisco Veterans Affairs Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Peripheral arterial disease (PAD) affects over 20% of aged adults and is very common among Veterans due significant tobacco use. PAD is due to the progressive blockage of peripheral arteries, predominantly to the legs, and results in intermittent claudication (IC) or recurrent muscle pain with activity secondary to insufficient blood supply. Those with PAD and IC experience a progressive decline in walking and poor quality of life. There is no effective medical treatment for PAD and IC. Metformin is a safe and effective treatment for Type 2 diabetes but it can also reduce inflammation, oxidative stress, and improve energy requirements as well as improve blood flow to the legs. Therefore, the investigators will test the ability of Metformin to improve overall functional status, reduce PAD progression, and reduce systemic inflammation in Veterans suffering from PAD and IC in a randomized, placebo controlled trial: Metformin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC) Trial. The success of this trial may identify a safe and effective treatment for PAD and IC.
Detailed Description
This is a quadruple blinded randomized controlled trial. Therefore, the allocation of participants to either placebo or metformin is unknown by the participant, research personnel, investigator, or blinded statistician. A total of 200 participants will be randomized over the course of 3 years. Study drug is administered to participants after all inclusion and no exclusion criteria is confirmed, informed consent is completed, and they are randomized. Study drug is continued throughout for 6 months following randomization. Participants are prospectively observed and monitored for 12 months after randomization. The patients' involvement (study visits/study phone calls) will last 12 months. Then, for 5 years, the study team will do a medical chart review as outlined in the ICF and protocol. All main study endpoints are within the 12-month time point. Secondary endpoints including MACE and MALE - major adverse cardiac and major adverse limb events - are time to event end points which can continue beyond the 12-month study time frame and will inform not only the effect of metformin on IC but also the natural history of IC among patients enrolled in the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intermittent Claudication
Keywords
Peripheral artery disease, intermittent claudication, metformin, anti-inflammatory agents, clinical trial protocol, atherosclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two arm randomization to 1000mg metformin ER or placebo daily with 1:1 parallel randomization, Randomization stratification will be based on baseline Maximum Walking Distance on the 6 Minute Walk Test and smoking status
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a triple-blinded randomized controlled trial. Therefore, the allocation of participants to either placebo or metformin is unknown by the participant, research personnel, and investigator. The study statistician will not be blinded.
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin ER 1000mg
Arm Type
Experimental
Arm Description
daily by mouth
Arm Title
Matching placebo
Arm Type
Placebo Comparator
Arm Description
daily by mouth
Intervention Type
Drug
Intervention Name(s)
Metformin ER
Other Intervention Name(s)
Glucophage
Intervention Description
Oral medication typically used for Type 2 diabetes with presumed anti-inflammatory properties
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Matched to active study drug
Primary Outcome Measure Information:
Title
Maximal Walking distance on the 6 minute walk test
Description
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity
Time Frame
6 month
Secondary Outcome Measure Information:
Title
6 minute walk test
Description
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
Time Frame
6 month
Title
6 minute walk test
Description
This validated measure of functional status in PAD and IC is highly reproducible and the ideal measure of real-life walking capacity. The six minute walk test includes maximal walking distance, pain free walking distance, time to pain onset.
Time Frame
12 month
Title
Cardiopulmonary exercise test
Description
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
Time Frame
6 month
Title
Cardiopulmonary exercise test
Description
The CPET is a well validated, reproducible measure symptom-limited (maximal) aerobic and anaerobic capacity in patients with PAD and IC and correlates with systemic disease severity and outcome
Time Frame
12 month
Title
EndoPAT
Description
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Time Frame
6 month
Title
Grip Strength
Description
Grip strength with a dynamometer provides a digital reading of force
Time Frame
6 month
Title
EndoPAT
Description
Systemic endothelial cell function and health will be evaluated by EndoPAT, measuring peripheral artery tonometry and generates reproducible digital pulse wave amplitude before and during reactive hyperemia induced by brachial artery occlusion with a blood pressure cuff
Time Frame
12 month
Title
Grip Strength
Description
Grip strength with a dynamometer provides a digital reading of force
Time Frame
12 month
Title
Ankle brachial index and pulse volume recording
Description
The ABI and PVR assess regional lower extremity blood supply in large-vessels and contribution of collaterals
Time Frame
6 month
Title
Ankle brachial index
Description
The ABI assesses regional lower extremity blood supply in large-vessels and contribution of collaterals
Time Frame
12 month
Title
Health related quality of life questionnaire
Description
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire [VascQol6]) health related quality of life questionnaires.
Time Frame
6 month
Title
Health related quality of life questionnaires
Description
Functionality outcomes will be supported by the general (SF-36) and disease specific (Vascular Quality of Life Questionnaire [VascQol6]) health related quality of life questionnaires.
Time Frame
12 month
Title
Walking Impairment Questionnaire
Description
A subjective measure of patient-reported walking performance developed for PAD
Time Frame
6 month
Title
Walking Impairment Questionnaire
Description
A subjective measure of patient-reported walking performance developed for PAD
Time Frame
12 month
Title
Freedom from major cardiac and major limb events
Description
Major cardiac events include: composite of CVD mortality, myocardial ischemia, coronary revascularization, hospitalization for heart failure, non-fatal stroke, and transient ischemic attack. Major adverse limb events include: composite of minor and major amputations, revascularization
Time Frame
12 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and Female Veteran >35 & <89
Symptoms of Intermittent claudication
Medically stable, optimal medical therapy (for >3 months prior to randomization which includes - statin and anti-platelet therapy, blood pressure control, smoking cessation and physical activity counseling)
a. Participants may not comply with the above measures to meet inclusion criteria, but investigator driven attempts to maximize the optimal medical therapy, as tolerated, for each participant prior to trial enrollment
PAD as defined by ABI <0.9 or >0.9 with evidence of PAD as documented by pulse volume recordings (within 6 months prior to expected randomization date)
Maximum Walking Distance (MWD) on the 6-minute walk test (6MWT) of greater than or equal to 50 meters with onset of pain before or at 400 meters without the use of a walker (cane is acceptable; within 6 months of expected randomization date)
Exclusion Criteria:
Diabetes (Type I or II) or Hemoglobin A1c>6.5 (within 6 months of expected randomization)
Currently Taking metformin or have previously taken metformin (within 6 months of enrollment)
Medical condition that limit their ability to ambulate other than PAD (i.e., Angina, CHF, pulmonary disease requiring oxygen, malignancy requiring treatment, etc.)
Prior above or below knee amputation
Critical limb threatening ischemia (i.e., non-healing wounds or rest pain)
Planned hospital admission, major operation, or lower extremity revascularization to be completed (within 12 months after expected randomization date)
Prior major operation or lower extremity revascularization (within the 3 months before expected randomization)
Unable to complete quality of life testing due to Non-English Speaking and/or Dementia
Kidney disease - dialysis or eGFR<45 (within 6 months of expected randomization date)*
Planned iodinated contrasted study (within 6 months of expected randomization date)
Evidence current or history of hepatic failure
Women who are pregnant or breast feeding
Unable to swallow uncrushed pills
Investigator expects inclusion could cause harm to subject
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Edith I Tzeng, MD
Phone
(412) 360-1657
Email
Edith.Tzeng@va.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine M Reitz
Phone
(412) 688-6000
Email
reitzkm2@upmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edith I. Tzeng, MD
Organizational Affiliation
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15240
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan L Barr
Phone
412-360-2387
Email
susan.barr2@va.gov
First Name & Middle Initial & Last Name & Degree
Samantha A Bonant, BS
Phone
(412) 360-3788
Email
samantha.bonant@va.gov
First Name & Middle Initial & Last Name & Degree
Edith I. Tzeng, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
MetfOrmin BenefIts Lower Extremities With Intermittent Claudication
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