Clinical Research Directory

Title: ICARUS - Psycho-physiological Profiling of Low and High Heat-resilient Individuals

The escalating environmental heat-stress associated with global warming is a societal challenge with large and potential harmful consequences for humans. Excess morbidity and mortality during heat waves provides strong evidence for fatal outcomes. However, it is unclear why some people are particularly vulnerable and get sick from hyperthermia, while others adapt and tolerate exposure. The Icarus project aims to provide a psycho-physiological framework for improved mitigation of the health threats associated with global warming. Combining expertise in integrative thermal physiology, pharmacology, photobiology, psychology and machine learning, we will collaborate on comprehensive cross-scientific studies using controlled lab-exposure combined with investigations in ecological settings including vulnerable and highly tolerant people across populations from northern to southern Europe. Advanced algorithms will be developed to generate personalized alerts and advising based on behavioral patterns, psychological profiling, predicted vulnerability and willingness to adopt resilience-building strategies. Global warming is projected to continue towards the end of the 21st century and constitutes an increasing threat to human health unless we as individuals and collectively become better in preventing acute effects, as well as devise sustainable strategies to limit further anthropogenic warming of the climate system. Acutely, improved guidance is important for both individual and public health, where Icarus aims at providing a highly improved basis for preventing heat-related disease, advising or nudging people towards pro-health behavior, including smarter use of technologies to mitigate heat stress, or adjusting medication to reduce adverse effects during heat events. In support of the sustainability agenda, our framework also forms a novel basis for developing advising algorithms relevant for optimization of climate change mitigation policy-making.

IEEM-Heat and Heart Failure

We will test the hypothesis that increasing skin wetness, and thus evaporative cooling, will attenuate the increase in core body temperature and accompanying cardiac stress during heat wave conditions in individuals with congestive heart failure. Secondly, we propose that wearing a water-saturated T-shirt will also be beneficial to attenuate the increase in core body temperature and accompanying cardiac stress during heat wave conditions in individuals with congestive heart failure. To accomplish these objectives, individuals with congestive heart failure and otherwise healthy control individuals will be exposed to the simulated heat wave condition (hot and dry) with the following cooling modalities: A) control trial (no limb immersion or skin wetting), B) skin wetting only trial, and C) water-saturated T-shirt trial in a randomized crossover fashion. Thermoregulatory and cardiovascular responses will be evaluated throughout these simulated heat wave exposures. Primary outcomes variables will be skin and core temperatures, while secondary variables will include measures of cardiovascular stress, myocardial perfusion, heart rate, and echo-based measures of cardiac function.

The Effectiveness of Emergency Room Protocols for Treating Hyperthermia

This study will help us as scientists and clinicians understand how effective commonly used cooling protocols in emergency departments are and which of the protocols is the most effective. It consists of a single, approximately 1 hour preliminary session and five, approximately 3 hour experimental sessions, equaling an approximate 16 hour total time commitment. The purpose of this research is to test the effectiveness of three cooling protocols. 1. Cooling packs 2. "Ice Sheets", which are bed sheets soaked in ice water, wrapped around the participant, while a fan blows air on them. 3. Body bag filled with ice, commonly used in emergency departments to treat hyperthermia Additionally, a negative control (passive cooling in air-conditioned room) and a positive control (cold water immersion).

Predicting Responses to Exhausting, Prolonged, And Repeated Exercise Demands (PREPARED) for Heat

The overall goal of this project is to identify a work/rest cycle that allows for faster mission completion needed in emergency situations, compared to current Army heat guidance, while mitigating heat strain and neuromuscular fatigue. This project will determine the trade-off between faster mission completion and risk of heat strain and physical performance decrements. Completion of this project will allow military leaders to make informed decisions by understanding the impact of their choices on the magnitude of physical performance decrements and expected heat casualties, setting up hot weather missions for success.

Heat Waves and the Elderly - Cooling Modalities

The purpose of this study is to assess how well cooling modalities work in reducing cardiovascular stress of the elderly to heat wave conditions

Postoperative Re-irradiaTion With and Without HYPERthermia: Toxicity, Quality of Life and Survival in Patients With Locoregional Recurrent Breast Cancer

In the Netherlands, breast cancer patients with locoregional recurrence (LRR) and high-risk factors are treated with postoperative re-irradiation with or without hyperthermia. Retrospective studies showed that 3-year locoregional control after postoperative re-irradiation with hyperthermia was 68-83%, and severe toxicity in up to 40% of LRR patients. Unfortunately, no prospective (randomized) data are available on clinical outcomes. Consequently, variation exists in hyperthermia-treatment and re-irradiation schedules. Prospective real-world data on oncological outcomes, toxicity and quality of life is highly needed for shared decision-making between patients and professionals. These data will be used in the design of a future randomized trial comparing postoperative re-irradiation and hyperthermia-treatment in high-risk LRR patients.

IEEM- Work:Rest Cycles in Burn Survivors- Humidity

The purpose of this project is to identify the effects of a severe burn injuries in humans on core temperature responses during work:rest cycles while in a heated environment.

Analysis of Hyperthermia as an Adjunctive Treatment to Evidence-based Clinical Intervention in Subjects With Plantar Fasciitis: a Double-blind Randomized Clinical Trial

This project aims to analyze the use of hyperthermia within a treatment protocol for plantar fasciitis, as well as to determine the difference between two and three sessions per week. Study participants will be divided into four intervention groups: the first will receive two sessions per week for a period of six months, while the second will receive three sessions per week for the same period. The treatment protocol will consist of therapeutic physical exercise focused on the foot muscles and stretching the plantar fascia and posterior chain, hyperthermia on the plantar fascia insertion area in the calcaneus and adjacent areas, and the use of an orthotic insole used for walking. The third and fourth intervention groups will receive the same treatment as mentioned above, but without hyperthermia. The third group will receive three sessions per week, while the second group will receive two sessions per week. Two different types of measurement variables will be used: objective variables will be used to measure local pain using an algometer, assess ankle joint range of motion, and use ultrasound imaging techniques. Subjective variables will also be used through validated questionnaires, which will address physical activity, perceived functional limitations in patients with lower limb pathologies, lower limb functional assessment, and a visual analogue scale for pain perception.

Hyperthermia in Patients With Chronic Primary Pain - Effects on Thermoregulation, Somatosensory System and Movement Evoked Pain

This study, in a quasi-experimental pre-post design, investigates the effect of serial water-filtered whole-body hyperthermia on circadian core body temperature, the somatosensory system (nociception) and pain perception in healthy and patients with chronic primary pain (e.g., fibromyalgia). The intervention lasts 3 weeks with two treatment sessions per week.

Analysis of Hyperthermia as an Adjunctive Treatment to Evidence-based Clinical Intervention in Subjects With Bursitis: a Double-blind Randomized Clinical Trial

This project aims to analyze the use of hyperthermia within a bursitis treatment protocol, as well as to determine the difference between two and three sessions per week. Study participants will be divided into four intervention groups: the first will receive two sessions per week for a period of six months, while the second will receive three sessions per week for the same period. The treatment protocol will consist of therapeutic physical exercise focused on the affected joint, stretching of the involved muscles, and the application of hyperthermia to the bursa and surrounding areas. The third and fourth intervention groups will receive the same treatment as mentioned above, but without hyperthermia. The third group will receive three sessions per week, while the second group will receive two sessions per week. Two different types of measurement variables will be used: on the one hand, the objective variable will be measurement and assessment of the bursa using ultrasound imaging. Subjective measurement variables will also be used through validated questionnaires, which will address physical activity, perceived functional limitations, and the visual analog scale for pain perception.

Skin Surface and Intradermal Temperature Responses to Heat Stress

The purpose of this study is to compare surface and intradermal skin temperature responses to heat stress with and without evaporative and convective cooling.

Cooling Solutions for Outdoor Workers

The investigators aim to test the effectiveness of two cooling interventions in reducing the core temperature of outdoor workers.

Work Design Interventions for Older Workers During Consecutive Days in the Heat

The goal of this project is to compare different ways to schedule a workday to see if older workers should follow a specific work protocol to reduce strain on the heart and muscles across two consecutive days of work. Participants will come to the lab a total of six times. During four of the visits participants will complete a box carrying task, simulating unloading a delivery truck. This will take place in a hot and humid room to simulate being outdoors during the summer.

Work Design Interventions for Heat Resilience

The goal of this project is to compare different ways to schedule a workday to see if older workers should follow a specific work protocol to reduce strain on the heart and muscles. Participants will come to the lab a total of six times. During four of the visits participants will complete a box carrying task, simulating unloading a delivery truck. This will take place in a hot and humid room to simulate being outdoors during the summer.

Enhancing Heat Resiliency in Older Adults During Indoor Overheating Via Heat Acclimation by Warm Water Immersion

As overheating in buildings is expected to increase as global warming continues, proactive measures to increase heat resiliency in heat-vulnerable older people are needed, especially for those without access to home cooling or reliable sources of electricity. While short-term heat acclimation through exercise in the heat has been shown to increase heat dissipation and decrease both the physical and mental stress imposed on individuals exposed to heat, such protocols are not tenable for older, sedentary adults. A recent report showed that seven consecutive days of warm-water immersion improved whole-body heat loss and reduced physiological strain as assessed during an exercise-heat stress in habitually active older men This represents a critical finding as an increase heat-loss capacity would serve as an important safeguard for older adults exposed to indoor overheating due to lack of air-conditioning. While this preliminary data highlights passive hot water immersion as a promising strategy for increasing heat-resilience in vulnerable adults, work is needed to confirm its efficacy in more "real-world" environments. Thus, this study aims to assess the effectiveness of a 7-day passive heating (warm-water immersion with core temperature clamped at \~38.5°C for the final 60 minutes) protocol in mitigating increases in thermal and cardiovascular strain in older females exposed to daylong (10-hours) indoor overheating (36°C, 45% relative humidity) prior to and following the passive heating intervention. Relative to males, females have a reduced heat loss capacity (\~5%), which is driven by differences in the activation of heat loss responses (i.e., skin blood flow and sweating). Although there have been mixed findings with regards to the influence of sex as a mediating factor for heat-related mortality, some studies suggest that females are at a higher risk of heat-related mortality and morbidity compared to males, especially amongst older individuals (≥65 years). Notably, a greater proportion of older females died compared to their male counterparts during the 2021 Western Heat Dome. While the underlying causes for these differences remain unclear, greater cardiovascular strain may place females at higher mortality risk during extreme heat.

Analysis of Hyperthermia as a Complementary Treatment to Evidence-based Clinical Intervention in Subjects With Carpal Tunnel Syndrome:

This project aims to analyze the use of hyperthermia within a treatment protocol for Carpal Tunnel Syndrome (CTS), as well as to determine the difference between two and three sessions per week. Study participants will be divided into four intervention groups: the first will receive two sessions per week for a period of six months, while the second will receive three sessions per week for the same period. The treatment protocol will consist of therapeutic physical exercise focused on the hand flexor muscles and neural stretching, the application of hyperthermia to the carpal tunnel and adjacent areas, and the use of a night splint. The third and fourth intervention groups will receive the same treatment as mentioned above, but without hyperthermia. The third group will receive three sessions per week, while the second group will receive two sessions per week. Two different types of measurement variables will be used: objective variables will be used to measure hand flexor muscle strength and wrist free range of motion. Subjective variables will also be used through validated questionnaires covering physical activity, perceived functional limitations, upper limb functional assessment, neuropathic pain, and a visual analogue scale for pain perception.

Impact of Extreme Heat on Myocardial Blood Flow and Flow Reserve in Young and Older Adults

Extreme heat causes a disproportionate number of hospitalizations and deaths in older adults relative to any other age group. Importantly, many hospitalizations and deaths are primarily due to cardiovascular events such as myocardial infarction. Previous data indicate that older adults have attenuated skin blood flow and sweating responses when exposed to heat, resulting greater increase in core body temperature. Despite these observations, relatively little is known about the risk for myocardial ischemia potentially contributing to the aforementioned higher morbidity and mortality in older adults during heat waves. The broad objective of this work is to determine the impact of ambient heat exposure on myocardial blood flow and flow reserve in young and older adults. Aim 1 will test the hypothesis that older adults exhibit attenuated myocardial flow reserve compared to young adults during heat stress. Aim 2 will determine if the percent of maximal myocardial flow reserve (assess via vasodilator stress) during heat exposure is higher in older adults compared to young adults. The expected outcome from this body of work will improve our understanding of the consequences of aging on cardiovascular responses to ambient heat stress.

Preparing for Heat Waves - Enhancing Human Thermophysiological Resilience

As the ongoing progression of climate change exposes individuals to elevated temperatures and an escalating frequency of extreme heat events, the risk of more intense and prolonged heat waves raises significant concerns for public health, particularly among vulnerable populations. The physiological response to acute heat stress involves involuntary thermolytic reactions that may strain the cardiovascular system, especially in individuals with pre-existing vulnerabilities. Heat acclimation has been identified as a potential strategy to enhance thermoregulation and mitigate the adverse effects of heat stress. While existing research primarily focuses on athletes and military, this study aims to investigate the impact of a practical heat acclimation strategy, combining passive and active heat exposure, on thermophysiological, cardiovascular and metabolic parameters in healthy overweight adults. The study targets a population at increased risk for heat-related complications, seeking to provide realistic guidelines for broader application when a heat wave appears on the weather forecast.

Prospective Hyperthermia Database in Cancer Patients (HT Register)

This monocentric study registry records all cancer patients at the Charité which are treated with hyperthermia to examine the therapeutic use of hyperthermia in cancer patients in the general application and to obtain an accurate risk-benefit balance After confinement in this database are the patients prospectively in order to complications, disease status and survival status tracked. Furthermore there is the possibility in the course of this study to an optional take part in translational accompanying research with the aim of prognostic factors for response to hyperthermia treatment.