Metformin and Muscle Recovery

Muscle Atrophy or Weakness Clinical Trial

Official title: Use of Metformin to Improve Muscle Regrowth in Older Adults

Status Not yet recruiting

Clinical Trial Summary

A hallmark of aging is an impaired ability to adequately recover following a stressor, such as muscle disuse, resulting in muscle fibrosis and weakness thereby increasing the risk for falls and loss of independence. Mechanistic-based therapeutic strategies to enhance muscle recovery in older adults do not exist. Metformin has been implicated to have positive effects on muscle size and function through non-glycemic mechanisms. Metformin has been shown to enhance macrophage function and lessen cellular senescence burden by targeting SASP in a variety of muscle interstitial cells. However, the role of metformin to improve muscle recovery in older adults following disuse atrophy through immunomodulating and senomorphic mechanisms have not been examined. Therefore, the purpose of this study is to conduct a randomized, double blind, placebo-controlled clinical trial in older adult participants to determine if short-term metformin delivery (vs placebo) during the recovery phase following disuse atrophy can improve muscle regrowth.

Clinical Trial Description

Aging is associated with impaired muscle recovery following disuse atrophy. If not addressed, restricted muscle regrowth and function may lead to a cascade of health crisis events for the aged individual (falls, disability, metabolic diseases). Clinically adopted treatments that promote muscle recovery, particularly in elderly patients, do not exist. The long-term goal of this project is to develop mechanistic-based therapeutic approaches to accelerate muscle recovery following disuse atrophy in older adults.

Macrophages are well understood to play a requisite role in myofiber remodeling including removal of debris and senescent cells, promotion of stem/satellite cell proliferation and differentiation, and regulation fibro-adipogenic progenitor cell (FAP) dynamics and fate. It is known that aged muscle during recovery have an impaired macrophage inflammatory and functional response complimented with poor muscle recovery. The investigators posit that age-related local immune dysfunction disrupts extracellular matrix (ECM) remodeling following muscle disuse by reducing the removal of senescence cells resulting in their accumulation. Therefore, treatments are needed to improve macrophage function and mitigate cellular senescence to facilitate muscle cellular remodeling events (e.g., macrophage, satellite cells, FAPs) during recovery following disuse in aging.

Metformin has gained traction to be repurposed as a treatment for a broad range of age-related diseases but its role in regulating muscle regrowth following disuse atrophy in humans is not known. Metformin has shown to modulate inflammatory profiles, mitigate cellular senescence and SASP (e.g., macrophages, FAPs, and myoblasts) while also improving muscle regeneration and satellite cell function in injured mice. Therefore, metformin treatment could have therapeutic value to temper unwanted collagen deposition and promote muscle regrowth and function when strategically delivered during the muscle regrowth phase in aging by targeting immune cell function and cellular senescence and SASP.

The overarching hypothesis is that metformin would mitigate cellular senescence and SASP specifically in macrophages, FAPs and satellite cells and would correspond to enhanced muscle function following disuse atrophy. The investigators will conduct a randomized, placebo-controlled clinical trial in healthy older participants to test if metformin provided during a 14d recovery phase following unilateral limb immobilization would improve muscle macrophage, FAP and satellite cell function, reduce cellular senescence and muscle fibrosis. ;

Related Conditions & MeSH terms

• Muscle Atrophy or Weakness
• Muscular Atrophy

• NCT number: NCT06185179
• Study type: Interventional
• Source: University of Utah
• Contact: Micah Drummond
• Phone: 801-213-2737
• Email: micah.drummond@hsc.utah.edu
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: September 1, 2024
• Completion date: July 31, 2030