Clinical Trials Logo

Clinical Trial Summary

Muscle atrophy and insulin resistance are common after bed rest in healthy older adults. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistance adults though the mechanisms are not fully known. Metformin used as a preventive strategy to maintain muscle and metabolic health in bed ridden older adults has not been investigated.


Clinical Trial 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: 1. 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. 2. 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. 3. Determine if muscle ceramides and insulin resistance return to baseline levels following 7 days of recovery after bed rest in the placebo group. 4. Determine if metformin given over a 2 week period (independent of bed rest) will improve muscle size, strength and insulin sensitivity. 5. 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 Design


Related Conditions & MeSH terms


NCT number NCT03107884
Study type Interventional
Source University of Utah
Contact
Status Active, not recruiting
Phase Early Phase 1
Start date August 1, 2019
Completion date April 30, 2025

See also
  Status Clinical Trial Phase
Completed NCT03142633 - MicroRNA as Biomarkers for Development of Metabolic Syndrome in Women With Polycystic Ovary Syndrome
Recruiting NCT04984226 - Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD Phase 2
Recruiting NCT05354245 - Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (DISTAL) N/A
Completed NCT03383822 - Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance Phase 1/Phase 2
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Suspended NCT03652987 - Endocrine and Menstrual Disturbances in Women With Polycystic Ovary Syndrome (PCOS)
Completed NCT04203238 - Potato Research for Enhancing Metabolic Outcomes N/A
Recruiting NCT03658564 - Preoperative Oral Carbohydrate Treatment Minimizes Insulin Resistance N/A
Completed NCT04183257 - Effect of Escalating Oral Vitamin D Replacement on HOMA-IR in Vitamin D Deficient Type 2 Diabetics Phase 4
Completed NCT04117802 - Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome N/A
Completed NCT03627104 - Effect of Dietary Protein and Energy Restriction in the Improvement of Insulin Resistance in Subjects With Obesity N/A
Completed NCT05124847 - TREating Pediatric Obesity N/A
Active, not recruiting NCT03288025 - Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) N/A
Completed NCT03809182 - Effect of Dexmedetomidine on Postoperative Glucose and Insulin Levels. Phase 4
Completed NCT01809288 - Identifying Risk for Diabetes and Heart Disease in Women
Completed NCT04642482 - Synbiotic Therapy on Intestinal Microbiota and Insulin Resistance in Obesity Phase 4
Terminated NCT03278236 - Does Time Restricted Feeding Improve Glycaemic Control in Overweight Men? N/A
Not yet recruiting NCT06159543 - The Effects of Fresh Mango Consumption on Cardiometabolic Outcomes in Free-living Individuals With Prediabetes N/A
Withdrawn NCT04741204 - Metformin Use to Reduce Disparities in Newly Diagnosed Breast Cancer Phase 4
Not yet recruiting NCT05540249 - Pre-operative Carbohydrates in Diabetic Patients Undergoing CABG N/A