Cold Exposure

This multicenter prospective observational cohort study aims to investigate the association between cumulative cold-region exposure and adverse left ventricular remodeling and cardiovascular outcomes in patients with coronary artery disease undergoing successful percutaneous coronary intervention (PCI). Individual-level chronic cold exposure will be quantified primarily by cumulative months of residence, work, or other relevant exposure in cold regions during the 3 years preceding PCI. Additional exposure measures will include regional cold-wave days derived from meteorological records and winter outdoor occupational exposure. Participants will undergo baseline cardiovascular magnetic resonance (CMR), echocardiography, electrocardiography, and clinical and laboratory assessment after PCI. Echocardiography will be repeated at 6 months to assess left ventricular remodeling. Cardiovascular events will be prospectively collected during follow-up. The study will evaluate whether cumulative cold-region exposure is associated with distinct CMR phenotypes, adverse left ventricular remodeling, and major adverse cardiovascular events (MACE), and whether cold-exposure measures provide incremental prognostic information beyond conventional clinical, imaging, and electrocardiographic risk markers.

This clinical trial explores how repeated short-term cold exposure impacts the molecular and physiological function of brown adipose tissue (BAT), a thermogenic organ associated with improved cardiometabolic health. While intermittent cold exposure has been shown to increase BAT activity and mass, as measured by fluorodeoxyglucose (18F-FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans, the molecular adaptations within BAT and other thermogenic tissues including skeletal muscle and white adipose tissue (WAT) remain poorly understood. Healthy adults aged 18 to 40 years (6 males and 6 females) will participate in a 10-day cold acclimation protocol (2 hours per day using water-perfused cooling blankets). The primary objective is to determine how cold exposure alters cellular heterogeneity and gene expression in BAT, WAT, and skeletal muscle. Participants will undergo baseline assessments, including measurements of energy expenditure, core and skin temperature, muscle activity, and blood sampling, each performed in both warm and cold conditions. These assessments will be followed by dynamic total-body PET/CT imaging during cold exposure and tissue biopsies from BAT, subcutaneous WAT, and skeletal muscle. These procedures will be repeated after the cold acclimation protocol to evaluate physiological and molecular changes. Additional outcomes include changes in energy expenditure, cold tolerance, and immune cell responses induced by cold exposure.

This is a single-center, prospective, single-arm, open-label phase I exploratory study that plans to enroll 24 participants with solid malignancies. All participants will receive controlled cold exposure in addition to standard PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor-based standard combination therapy. A 2-day cold acclimation phase will precede formal intervention, consisting of approximately 20°C exposure for 8 hours on Day -2 and approximately 18°C exposure for 10 hours on Day -1. The first combination cycle begins on Day 1 concurrently with PD-1/PD-L1-based treatment, with exposure to an 18°C temperature-controlled hospital room for 12 hours per day for 7 consecutive days. If tolerated, cold exposure may be repeated in subsequent PD-1/PD-L1 treatment cycles. The primary objective is to evaluate safety, tolerability, and feasibility. Secondary objectives are to explore preliminary antitumor activity and the effects on brown adipose tissue activation, peripheral immune profiling, circulating cytokines, metabolomics, gut microbiota, patient-reported outcomes, and tumor immune/metabolic biomarkers when paired tumor tissue is available.

This clinical trial will assess the whether fish oil supplementation can modulate brown fat activation, shivering, thermal comfort and skin blood flow during cold exposure.

High daily energy expenditures without compensatory increases in energy intakes results in severe energy deficits during cold-weather military operations. Observational and experimental data from our laboratory suggests that consuming higher-fat, energy dense products can increase energy intake and attenuate energy deficits, however, laboratory analysis is needed to understand the impact of macronutrient manipulation on substrate oxidation and aerobic performance. This proof of concept, randomized crossover study will examine the effects of consuming an isocaloric bar (approximately 350 kcal) that is higher in carbohydrate (CHO: 50% carbohydrate, 30% fat, 20% protein) or higher in fat (FAT: 30% carbohydrate, 50% fat, 20% protein) on substrate oxidation and aerobic performance (time trial) during acute cold (5°C) exposure. Volunteers will wear shorts and a t-shirt during cold exposure, with continuous monitoring of core and skin temperatures. Baseline data will be collected on volunteer height, weight, body composition, and V̇O2peak. To ensure volunteers are familiar with exercise protocols, they will complete practice sessions of all exercise before the start of data collection. Exercise and diet will be controlled throughout data collection. 24 hours prior to data collection, volunteers will consume a lead-in study diet and will abstain from exercise. After 24 hours, volunteers will return to the laboratory for assessment of substrate oxidation and aerobic performance. Volunteers will consume the CHO or FAT treatment bars under cold conditions, followed by 60 minutes of rest prior to the start of exercise. Volunteers will then complete 90 minutes of load carriage steady-state (55 ± 5% VO2peak) treadmill exercise, wearing a ruck with weighing 30% of their total body mass. After steady-state exercise, aerobic performance will be assessed by having volunteers complete a 2-mile time trial. Indirect calorimetry will be used to determine substrate oxidation during steady-state exercise. Serial blood draws will be collected during each trial to assess circulating substrate/hormone responses. Protocol days will be separated by a minimum washout period of 6 days.