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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Department of Veterans Affairs
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01804049
First received: February 28, 2013
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Prediabetes
Drug: metformin
Drug: placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Metformin and Muscle in Insulin-resistant Older Veterans

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Change in total and appendicular lean mass [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Change in physical performance [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    At baseline, 1, 2, and 3 year follow-up visits, participants will have physical performance tests assessed including: (1) 6 meter timed walk, (2) 400 meter timed walk, (3) grip strength measured with a Jamar dynamometer, (4) timed task of rising from a chair 5 times in succession without use of arms, (5) timed tandem, semi-tandem and side-by-side stands.

  • Change in muscle histologic characteristics [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    At baseline and 1 year 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 following histologic measurements: (1) mitochondrial content, (2) triglyceride content, (3) capillary density, and (4) quantification of Type I, IIa and IIx muscle fibers.


Estimated Enrollment: 120
Study Start Date: April 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
60 participants will be randomized to placebo pills.
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.
Active Comparator: Metformin
60 enrolled participants will be randomized to metformin.
Drug: 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.
Other Name: Glucophage

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. Our 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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • We 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 6 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 eGFR<60 mL/min; liver dysfunction defined as ALT>48 U/L, AST>41 U/L or AlkPhos>141U/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 INR>1.2 or aPTT>36 seconds
  • Allergy to lidocaine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01804049

Contacts
Contact: Christine G Lee, MD Christine.Lee8@va.gov
Contact: Carrie Farrar, MPH (503) 494-4233 farrarc@ohsu.edu

Locations
United States, Oregon
VA Medical Center, Portland Recruiting
Portland, Oregon, United States, 97201
Contact: Michael P Davey, MD PhD    503-273-5125    michael.davey@va.gov   
Principal Investigator: Christine G. Lee, MD         
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Christine G. Lee, MD Portland VA Medical Center, Portland, OR
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01804049     History of Changes
Other Study ID Numbers: CLIN-019-12S
Study First Received: February 28, 2013
Last Updated: June 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
metformin
muscle
insulin resistance
sarcopenia
older adults
impaired fasting glucose

Additional relevant MeSH terms:
Metformin
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014