Metformin, Muscle Energetics, and Vascular Function in Older Adults With Peripheral Artery Disease

NCT01901224 | Terminated Phase 4 Results

• 1 other identifier: 2013P001042
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Peripheral Artery Disease

Outcome Measures

Primary Outcomes (1)

• Change in PCr Recovery Time

  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 Outcomes (1)

• Change in Flow-mediated Dilation (FMD)

  baseline, 12 weeks

Other Outcomes (4)

• Change in Maximal Treadmill Walking Time

  baseline, 12 weeks

• Change in Pain-free Treadmill Walking Time

  baseline, 12 weeks

• Change in Oxygen Consumption

  baseline, 12 weeks

Study Arms (2)

Metformin 1000 mg

EXPERIMENTAL

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.

Drug: Metformin 1000 mg

Control

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Metformin 1000 mg DRUG

Metformin 1000 mg

Placebo DRUG

Control

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 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%

You may not qualify if:

• 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
• hour Oral Glucose Tolerance Test (OGTT) \> 200 mg/dL

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

Metformin

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Mark A. Creager, MD
• Organization: Brigham and Women's Hospital

mark.a.creager@hitchcock.org

603-650-8283

Study Officials

• Mark A Creager, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mark A. Creager, MD

Study Record Dates

• First Submitted: July 12, 2013
• First Posted: July 17, 2013
• Study Start: July 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: September 24, 2018
• Results First Posted: September 24, 2018

Record last verified: 2018-09

Locations

US (1)