PrediabetesPhase 1/2M&MNCT01804049
Metformin and Muscle in Insulin-resistant Older Veterans
A Phase 1/2 study testing metformin in people with Prediabetes, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Prediabetes
- What is being tested?
- metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2014to 31 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Portland Health Care System, Portland, OR
Portland, Oregon, 97239
About this study
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.
Read the 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
- Being tested
- metformin, placebo
- Keywords
- metformin, muscle, insulin resistance, sarcopenia, older adults, impaired fasting glucose
- Medical subject headings
- Prediabetic State, Insulin Resistance, Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metforminDrug
Also called Glucophage
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.
placeboDrug
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 group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 60 participants will be randomized to placebo pills. Receives: Drug: placebo |
| Metformin | Active comparator | 60 enrolled participants will be randomized to metformin. Receives: Drug: metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (2)
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.
Measured: 3 years
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2013 (estimated)
- Study start8 Apr 2014
- Primary completion31 Aug 2018
- Study completion31 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PrediabetesStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- Oregon Health and Science University
- Responsible party
- Sponsor
- Investigators
- Robert F Klein, Principal investigator, VA Portland Health Care System, Portland, OR
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01804049
- Sponsor's protocol ID
- CLIN-019-12S
- Acronym
- M&M
- Status last verified
- Feb 2020
- First submitted
- 28 Feb 2013
- Last updated
- 11 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin and Muscle in Insulin-resistant Older Veterans
- ClinicalTrials.gov ID
- NCT01804049
- Acronym / sponsor ID
- M&M / CLIN-019-12S
- Conditions
- Prediabetes
- Keywords
- metformin, muscle, insulin resistance, sarcopenia, older adults, impaired fasting glucose
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- Oregon Health and Science University
- Study start
- 8 Apr 2014 (actual)
- Primary completion
- 31 Aug 2018 (actual)
- Study completion
- 31 Aug 2018 (actual)
- First posted
- 5 Mar 2013 (estimated)
- Results
- Posted 11 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: placebo60 participants will be randomized to placebo pills. |
| Metformin | Active comparator | Drug: metformin60 enrolled participants will be randomized to metformin. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metforminAlso: GlucophageMetformin 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. | Drug | Metformin |
| placeboOne placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study. | Drug | Placebo |
Primary outcome
Change in Total Lean Mass From Baseline
Time frame: 3 years
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.
2 secondary outcomes
Change in Physical Performance - 400 Meter Walk Speed
Time frame: 3 years
Change in Muscle Characteristics
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert F Klein principal investigator
VA Portland Health Care System, Portland, OR
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing metformin in people with Prediabetes, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Total Lean Mass From Baseline (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2020.