search
Back to results

Metformin and Muscle in Insulin-resistant Older Veterans (M&M)

Primary Purpose

Prediabetes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
metformin
placebo
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Prediabetes focused on measuring metformin, muscle, insulin resistance, sarcopenia, older adults, impaired fasting glucose

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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)

For the muscle biopsy substudy, additional exclusion criteria include:

  • 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

Sites / Locations

  • VA Portland Health Care System, Portland, OR

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Metformin

Arm Description

60 participants will be randomized to placebo pills.

60 enrolled participants will be randomized to metformin.

Outcomes

Primary Outcome Measures

Change in Total Lean Mass From Baseline
At baseline, 1, 2, and 3 year follow-up visits, participants will have whole body dual x-ray absorptiometry scans (DXA) with a Hologic QDR 4500W DXA scanner by a certified DXA operator to determine total body lean mass and appendicular lean mass (Kg). The changes in appendicular and total lean mass were calculated by determining the change from baseline to the three year data point. If participants withdrew from the study prior to collection of 3 year data, the final time point available was used.

Secondary Outcome Measures

Change in Physical Performance - 400 Meter Walk Speed
At baseline, 1, 2, and 3 year follow-up visits, participants will have physical performance assessed using a 400 meter timed walk. We report the 400 meter timed walk speed as the change from baseline in seconds. The change in walk speed from baseline to the three year time point was used for analysis. For participants who withdrew from the study early, the walk speed from the final data point collected was used.
Change in Muscle Characteristics
At baseline and 6 month follow-up visits, 32 subjects will undergo a muscle biopsy of the vastus lateralis muscle 15 cm above the patella using the modified Bergstrom technique under local anesthesia. The muscle biopsy specimens will be used for the histochemical and transcriptome analyses

Full Information

First Posted
February 28, 2013
Last Updated
February 4, 2020
Sponsor
VA Office of Research and Development
Collaborators
Oregon Health and Science University
search

1. Study Identification

Unique Protocol Identification Number
NCT01804049
Brief Title
Metformin and Muscle in Insulin-resistant Older Veterans
Acronym
M&M
Official Title
Metformin and Muscle in Insulin-resistant Older Veterans
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
April 8, 2014 (Actual)
Primary Completion Date
August 31, 2018 (Actual)
Study Completion Date
August 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
Oregon Health and Science University

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.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prediabetes
Keywords
metformin, muscle, insulin resistance, sarcopenia, older adults, impaired fasting glucose

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
60 participants will be randomized to placebo pills.
Arm Title
Metformin
Arm Type
Active Comparator
Arm Description
60 enrolled participants will be randomized to metformin.
Intervention Type
Drug
Intervention Name(s)
metformin
Other Intervention Name(s)
Glucophage
Intervention Description
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
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Total Lean Mass From Baseline
Description
At baseline, 1, 2, and 3 year follow-up visits, participants will have whole body dual x-ray absorptiometry scans (DXA) with a Hologic QDR 4500W DXA scanner by a certified DXA operator to determine total body lean mass and appendicular lean mass (Kg). The changes in appendicular and total lean mass were calculated by determining the change from baseline to the three year data point. If participants withdrew from the study prior to collection of 3 year data, the final time point available was used.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Change in Physical Performance - 400 Meter Walk Speed
Description
At baseline, 1, 2, and 3 year follow-up visits, participants will have physical performance assessed using a 400 meter timed walk. We report the 400 meter timed walk speed as the change from baseline in seconds. The change in walk speed from baseline to the three year time point was used for analysis. For participants who withdrew from the study early, the walk speed from the final data point collected was used.
Time Frame
3 years
Title
Change in Muscle Characteristics
Description
At baseline and 6 month follow-up visits, 32 subjects will undergo a muscle biopsy of the vastus lateralis muscle 15 cm above the patella using the modified Bergstrom technique under local anesthesia. The muscle biopsy specimens will be used for the histochemical and transcriptome analyses
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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) For the muscle biopsy substudy, additional exclusion criteria include: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert F Klein
Organizational Affiliation
VA Portland Health Care System, Portland, OR
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Portland Health Care System, Portland, OR
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Metformin and Muscle in Insulin-resistant Older Veterans

We'll reach out to this number within 24 hrs