- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03107884
Role of Metformin on Muscle Health of Older Adults
Metformin to Prevent Inactivity-induced Loss of Muscle Health During Aging
Study Overview
Status
Conditions
Detailed Description
Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the "new normal", ultimately increasing the risk of skeletal muscle and metabolic dysfunction (e.g. insulin resistance and sarcopenia).
Muscle atrophy and insulin resistance are an unfortunate consequence with disuse in older adults. We have observed with our bed rest studies in healthy older adults that in addition to muscle and metabolic changes, we notice increased skeletal muscle inflammation, impaired glucose uptake signaling and an upregulation of enzymes related to de novo ceramide biosynthesis. The accumulation of ceramide, a toxic lipid intermediate, can disrupt glucose homeostasis and impair muscle growth. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistant adults through a mechanism that may involve ceramide synthesis. Metformin used as a preventive strategy to maintain muscle and metabolic health during a period of physical inactivity in older adults has not been investigated.
A separate group of participants for the 2-week Metformin Run-in Period, independent of the bed rest and recovery study will also be recruited. All study procedures will be the same as the 2-week Run-In period within the full protocol.
We hypothesize that metformin treatment in healthy older adults during bed rest would attenuate inflammation, insulin resistance, and thigh muscle loss and changes in lipid accumulating in muscle. We also hypothesize that elevated skeletal muscle ceramide levels, is central to the development of insulin resistance with bed rest in older adults.
Therefore, we have proposed to conduct a clinical study in older adults to:
- Test if daily metformin treatment (vs placebo) during 5d of bed rest in older adults would attenuate intramuscular ceramide accumulation (lipid accumulation), insulin resistance (euglycemic-hyperinsulinemic clamp), and loss in thigh muscle lean mass. We would also like to determine if 5-days of bed rest in older adults within the placebo group increases skeletal muscle ceramide concentrations and whether these are in turn associated with insulin resistance.
- Test if daily metformin treatment (vs placebo) during 5d of bed rest in older adults would improve skeletal muscle glucose uptake cell signaling, reduce skeletal muscle inflammation and ceramide biosynthesis signaling.
- Determine if muscle ceramides and insulin resistance return to baseline levels following 7 days of recovery after bed rest in the placebo group.
- Determine if metformin given over a 2 week period (independent of bed rest) will improve muscle size, strength and insulin sensitivity.
- Determine if metformin improves the recovery of muscle size and strength and insulin sensitivity 7 days after bed rest.
These findings will be foundational for future development of treatments to prevent insulin resistance and muscle atrophy in inactive older adults.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Micah Drummond
- Phone Number: 801-585-1310
- Email: micah.drummond@hsc.utah.edu
Study Contact Backup
- Name: Brenda Northrup
- Phone Number: 801-382-8189
- Email: brenda.northrup@hsc.utah.edu
Study Locations
-
-
Utah
-
Salt Lake City, Utah, United States, 84108
- University of Utah
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 60y and older
- Ability to sign informed consent
- Free-living, prior to admission
Exclusion Criteria:
- Personal history of cardiovascular disease
- Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, HbA1c ≥6.5%)
- Evidence of kidney disease or failure (defined as serum creatinine > 1.5mg/dL)
- Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes)
- Risk of Deep vein thrombosis including family history of thrombophilia, Deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL)
- Use of anticoagulant therapy (e.g., Coumadin, heparin)
- Uncontrolled hypertension (e.g. systolic pressure >160 or a diastolic blood pressure > 100)
- Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
- Currently on a weight-loss diet or body mass index > 30 kg/m2
- Inability to abstain from smoking for duration of study
HIV or hepatitis B or C*
- Subjects excluded due to positive screening results, including HIV, hepatitis B or hepatitis C, will be immediately scheduled for counseling and follow-up testing as needed, and will be advised to consult their primary physician.
- Chronic systemic corticosteroid use (≥ 2 weeks) within 4 weeks of enrollment and for study duration (intra-articular/topical/inhaled therapeutic or physiologic doses of corticosteroids are permitted). Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement is permitted)
- Subjects with hemoglobin or hematocrit lower than accepted lab values
- History of stroke with motor disability
- A recent history (<12 months) of GI bleed
Depression [>5 on the 15 items Geriatric Depression Scale (GDS)]*
*This criteria will only apply to subjects in the bed rest arm.
- Liver disease (the ratio of serum aspartate aminotransferase to serum alanine aminotransferase 2 times above the normal limit, hyperbilirubinemia) History of respiratory disease
- Currently taking estrogen products (topical vaginal products are not exclusionary (e.g. cream))
- Recent travel history as defined by 4 hours of travel by airplane in the last week
- Any other condition or event considered exclusionary by the PI and faculty physician
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Metformin (Bed Rest)
Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day).
During bed rest, participants will be given 1 gram of metformin two times a day (morning and evening).
This dosage and frequency will occur during four consecutive days of bed rest.
|
A clinical oral dose of Metformin will be given to participant daily during bed rest
Other Names:
|
Placebo Comparator: Placebo (Bed Rest)
Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group.
During bed rest, participants will be given the same amount of pills and given at the same time of day (morning and evening) as the experimental group.
This strategy will occur during four consecutive days of bed rest.
|
Placebo-comparator.
The same quantity of non-active tablets will be given at the same time of day as the Metformin treatment group
|
Experimental: Metformin (2 week run-in only)
Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day).
These participants will not participate in the bed rest portion of the protocol.
|
A clinical oral dose of Metformin will be given to participant daily during a two week run-in period only.
Other Names:
|
Placebo Comparator: Placebo (2 week run-in only)
Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group.
These participants will not participate in the bed rest portion of the protocol.
|
Placebo-comparator.
The same quantity of non-active tablets will be given at the same time of day as the Metformin 2 week run-in treatment group.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Muscle size
Time Frame: Change in muscle size from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest
|
Change in muscle size from baseline to 5-days of bed rest (determined from MRI)
|
Change in muscle size from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest
|
Insulin sensitivity
Time Frame: Change in insulin sensitivity from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest
|
Change in insulin sensitivity from baseline to 5-days of bed rest (determined from glucose infusion rate)
|
Change in insulin sensitivity from baseline to 5-days of bed rest will be compared between groups after 5 days of bed rest
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Micah Drummond, University of Utah
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 93579
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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