Metformin and Muscle in Insulin-resistant Older Veterans

NCT ID: NCT01804049

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-08
• Study Completion Date: 2018-08-31

Brief Summary

Sarcopenia is the loss of muscle mass, strength and function with aging and is associated with increased disability, falls and fractures. Older adults with diabetes and prediabetes are insulin resistant and have a higher risk of developing sarcopenia. This study examines the use of metformin, an antidiabetic drug, for preventing the development of sarcopenia in older adults with prediabetes.

Detailed Description

The proposed study utilizes clinical and translational research approaches to study sarcopenia. Sarcopenia is common in older adults and is associated with decreased strength, increased disability, falls and fractures. There are currently few interventions to prevent or treat sarcopenia and a poor understanding of the mechanisms for sarcopenia. Given the growing number of Veterans over the age of 65, studies to prevent sarcopenia and resulting disability are important for the health, independence and well-being of this population. The investigators' preliminary studies have shown that older adults with diabetes have an accelerated loss in muscle mass and gait speed, except when treated with metformin. Older adults with prediabetes also have a greater decline in muscle mass and higher incidence of disability. Therefore, this study further investigates these findings by addressing the following aims: (1) to determine whether metformin can prevent the loss in muscle mass and physical performance and (2) to examine changes in muscle histologic characteristics associated with metformin treatment in older adults with prediabetes.

Conditions

Prediabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Placebo

60 participants will be randomized to placebo pills.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.

Metformin

60 enrolled participants will be randomized to metformin.

Group Type: ACTIVE_COMPARATOR

metformin

Intervention Type: DRUG

Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.

Interventions

metformin

Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.

Intervention Type: DRUG

placebo

One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility Criteria

Inclusion Criteria

• The investigators will enroll 120 sedentary, weight-stable, ambulatory Veterans aged 65 years and older with prediabetes identified with fasting glucose values 100 mg/dL or greater but under 126 mg/dL with no use of diabetes medications.
• Participants must demonstrate that they are able to ambulate 400 meters without assistance.

Exclusion Criteria

• Chronic medical conditions affecting muscle mass or function like active non-skin cancer and hypogonadism
• Medications affecting muscle mass or function like glucocorticoids and androgen/antiandrogens
• Contraindications to metformin such as renal dysfunction defined as creatinine >= 1.5 mg/dL for men or >=1.4 mg/dL for women or estimated glomerular filtration rate (eGFR)<60 mL/min; liver dysfunction defined as alanine aminotransferase (ALT)>48 U/L, aspart aminotransferase (AST)>41 U/L or alkaline phosphatase (AlkPhos)>141 U/L; B12 deficiency defined as B12 level <180 pg/dL; congestive heart failure; known hypersensitivity to metformin; excessive alcohol intake (average of 2 or more alcoholic beverages/day over a month)

• Conditions that include bleeding risk such as the use of warfarin, clopidogrel/ticlopidine, aggrenox, dabigatran or anagrelide; laboratory results showing platelets<150 billion/L or international normalized ratio (INR)>1.2 or activated partial thromboplastin time (aPTT)>36 seconds
• Allergy to lidocaine

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert F Klein

Role: PRINCIPAL_INVESTIGATOR

VA Portland Health Care System, Portland, OR

Locations

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CLIN-019-12S

Identifier Type: -

Identifier Source: org_study_id