A Prospective Study of Cold Exposure in Patients With MASH

Overview

This prospective, single-center, single-arm exploratory study aims to evaluate the safety, feasibility, and potential metabolic and hepatic effects of repeated cold exposure in patients with metabolic dysfunction-associated steatohepatitis (MASH). A total of 11 participants with MASH will undergo cold exposure using a water-perfused cooling suit once daily for approximately 120 minutes over a 3-month intervention period. Liver fat content, liver function, lipid metabolism, body weight, and body mass index will be assessed before and after the intervention. Liver fat content will be evaluated by magnetic resonance imaging proton density fat fraction (MRI-PDFF), and blood tests will include alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC). Liver ultrasound or liver stiffness-related measures and noninvasive fibrosis scores will also be evaluated when available. Safety, tolerability, adherence, and cold-related adverse events will be monitored throughout the study.

This is a single-center, single-arm, prospective, exploratory clinical study designed to investigate the feasibility, safety, and short-term effects of repeated cold exposure in patients with metabolic dysfunction-associated steatohepatitis (MASH). Eleven participants will be enrolled and will serve as their own controls, with clinical and metabolic parameters compared between baseline and the end of the intervention. Participants will undergo repeated cold exposure using a water-perfused cooling suit for 3 months. Cold exposure will generally be performed once daily for approximately 120 minutes. Each session will include a 10- to 15-minute adaptation period, during which the circulating-water temperature will be gradually reduced toward a target temperature of approximately 22°C according to individual tolerance. The actual circulating-water temperature, exposure duration, tolerability, and any adverse reactions will be recorded for each session. Blood pressure, heart rate, body temperature, shivering, and subjective discomfort will be monitored during the intervention. Baseline assessments will include clinical evaluation, blood biochemical testing, MRI-PDFF for liver fat quantification, liver ultrasound, and noninvasive liver fibrosis assessment. After completion of the 3-month intervention, these assessments will be repeated. Changes in MRI-PDFF, ALT, AST, TG, TC, body weight, and body mass index will be evaluated as major clinical outcomes. Additional assessments will include liver ultrasound or liver stiffness-related measures, noninvasive fibrosis scores such as FIB-4 and NFS, and FibroScan or equivalent liver stiffness assessment when available. Safety outcomes will include adverse events, serious adverse events, cold-related discomfort, and abnormalities in vital signs. Feasibility outcomes will include study completion, adherence, and actual duration of cold exposure. Dietary intake, physical activity, body weight, and concomitant medications will also be recorded during the study to assist with interpretation of the observed changes.