Metformin and Muscle in Insulin-resistant Older Veterans | RxWiki

Metformin and Muscle in Insulin-resistant Older Veterans

Overview[ - collapse ][ - ]

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	Prediabetes
Intervention	Drug: metformin Drug: placebo
Phase	Phase 1/Phase 2
Sponsor	Department of Veterans Affairs
Responsible Party	Department of Veterans Affairs
ClinicalTrials.gov Identifier	NCT01804049
First Received	February 28, 2013
Last Updated	January 15, 2014
Last verified	January 2014

Tracking Information[ + expand ][ + ]

First Received Date	February 28, 2013
Last Updated Date	January 15, 2014
Start Date	February 2014
Estimated Primary Completion Date	March 2018
Current 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).
Current 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Metformin and Muscle in Insulin-resistant Older Veterans
Official Title	Metformin and Muscle in Insulin-resistant Older Veterans
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. 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.
Study Type	Interventional
Study Phase	Phase 1/Phase 2
Study Design	Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)
Condition	Prediabetes
Intervention	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 Names: GlucophageDrug: 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.
Study Arm (s)	Placebo Comparator: Placebo 60 participants will be randomized to placebo pills. Active Comparator: Metformin 60 enrolled participants will be randomized to metformin.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	120
Estimated Completion Date	March 2018
Estimated Primary Completion Date	February 2018
Eligibility 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
Gender	Both
Ages	65 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Christine G Lee, MD Christine.Lee8@va.gov
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01804049
Other Study ID Numbers	CLIN-019-12S
Has Data Monitoring Committee	Yes
Information Provided By	Department of Veterans Affairs
Study Sponsor	Department of Veterans Affairs
Collaborators	Oregon Health and Science University
Investigators	Principal Investigator: Christine G. Lee, MD Portland VA Medical Center, Portland, OR
Verification Date	January 2014

Locations[ + expand ][ + ]