University of Utah will test whether metformin reduces cellular senescence and muscle fibrosis after knee ligament surgery
University of Utah will test whether metformin reduces cellular senescence and muscle fibrosis after knee ligament surgery
In a trial involving 40 patients who have undergone anterior cruciate ligament reconstruction, metformin will be compared with placebo. After four months, the researchers will take a thigh muscle biopsy and compare three outcomes: evidence of cellular senescence, scar tissue formation, and leg strength.
On July 13, University of Utah registered the project on ClinicalTrials.gov. Surgeons can restore knee stability after an anterior cruciate ligament tear, but the thigh muscle often loses mass and strength before rehabilitation is complete. The injury, surgery, and forced inactivity increase inflammation and collagen levels in the muscle. Collagen contributes to healing, but an excess produces fibrosis, a dense form of scar tissue that prevents the muscle from contracting normally.
The protocol asks a specific question about metformin in humans. Participants will receive either metformin or placebo for four months. The team will then compare knee extensor strength and two biopsy measurements: collagen content and the SA-β-galactosidase signal. This assay is often used to identify cells that have stopped dividing after injury or stress and remain in that state, which is known as cellular senescence.
The use of a biopsy changes what this study can test. A review of 27 human trials found that senescence-associated inflammatory proteins are detected in blood more often than direct evidence of senescent cells. These proteins can also rise during infection, excess weight, physical exertion, and normal healing. A SenCat marker map also showed that no single marker identifies senescent cells across all tissues. In this protocol, the SA-β-galactosidase signal is assessed alongside fibrosis and leg strength. The biopsy samples the muscle tissue that must recover directly.
Metformin is used to treat type 2 diabetes. In geroscience, researchers are also considering it as a possible intervention targeting metabolism and age-related inflammation. This protocol will test whether the drug helps a specific injured tissue recover with less fibrosis and a change in a cellular senescence marker.
Enrollment will begin in November, and the study will include 40 participants who have undergone this operation. Its findings will address muscle recovery in this group. The design links a tissue measurement to a functional test by asking whether reduced fibrosis is accompanied by restored leg strength.
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