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

March 27, 2026 updated by: Georgia Ntina, University of Thessaly

Physiological Phenotyping

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Warming of the climate system is ongoing and there is strong evidence for detrimental effects of environmental heat stress on human with impact on public health and quality of life for billions of people globally - with the most damaging effects on societies in the hottest parts of the world. However, recent heatwaves in Canada, USA, and Northern Europe saw temperatures surpassing 40°C. Documented impacts on mortality show how climate change and the associated geographical spread of heatwaves also have health consequences in regions previously spared from high temperatures. At the same time, cutaneous melanoma already is a documented and increasing public health concern and characterized by high incidence in fair-skinned populations of European descent, particularly in Central and North European countries. The incidence of 29.7 per 100,000 person-years in Denmark is the 3rd highest globally, compared to the world average of 3.4. Alarmingly, the World Health Organization (WHO) projects that the number of new cases of melanoma per year will increase by more than 50% from 2020 to 2040.

It is abundantly clear that certain populations are more vulnerable to global warming and that certain individuals within each population are more susceptible to heat-stress than others. In the Icarus project, we will find ways to identify these people and at a large scale protect using predictive algorithms. Achieving this ambition may save lives, reduce the burden on healthcare systems, support the global sustainability agenda including UN defined sustainability goals such as the prevention of poverty via improved productivity. Thus, public health, sustainability and economic benefits from this ambitious project are clear should it succeed.

The fatal outcome of exposure to extreme heat and sunlight, as described in the myth about Icarus and scientifically documented with epidemiological evidence for excess death rates during heatwaves is, however, only the tip of the iceberg in terms of public health problems and societal impact imposed by global warming. We have documented the occupational health burden, productivity losses and economic costs associated with elevated environmental heat and we have shed light on the interaction between heat stress and exposure to solar radiation. The later with major isolated health effects of ultraviolet radiation (UVR) on the skin. Our pilot observations from combined heat-radiation exposure studies indicate that some individuals, both before and after acclimatization, are very tolerant and show almost no detrimental effects on motor-cognitive performance; while others (healthy; matched for fitness and age) show drastic changes in clinical outcomes and major declines in physical and mental performance. It is well known that sunlight exposure, and in particular certain UVR wavelengths, has direct damaging effects on the skin, but there is a large knowledge gap on its interaction with thermal physiological effects. Also, there is no research on acclimatization effects and very limited understanding of the interaction between impacts on cognitive function and psychological/behavioral factors. This is central for understanding heat vulnerability at the individual level and how it subsequently affects public health - as those at highest risk become ill, hospitalized, or add to the mortality statistics. Furthermore, these interactions are fundamental for the development of a psychophysical framework and improve the ability to understand and subsequently influence collective behavior, which is highly relevant for the implementation of policies and climate change mitigation strategies.

Differences in heat vulnerability are also observed at the population-level with markedly lower temperature thresholds for excess mortality in North compared to South European countries, but it is largely unknown if this pronounced difference in heat resilience relates to a superior "physiological defense system" in South Europeans orprimarily relates to different social experiences of heat and thus different behaviors i.e., more appropriate thermoregulatory behavior in South Europeans. Higher risk taking (e.g., inappropriate "sun-bathing culture") is also a highly relevant factor in terms of skin damage (DNA mutation and photocarcinogenesis) and the associated risk for developing skin cancer. For instance, in a recent pilot study, we observed a 10-fold higher excretion of cyclobutane thymine dimers in the urine (as a marker of skin DNA damage) of Danish volunteers after a winter vacation to a sunny region, compared to their peers who freely chose to be less exposed.

Analogous to the mythical Icarus, who flew too close to the sun, our recent pilot data individual data from papers by our consortium show that vulnerable people, collectively translating into differences at the population level, arenot able to sense and comprehend the danger associated with exposure to solar radiation. If we - unlike Icarus' father - are to become better at protecting individuals atrisk and advise humanity at large, we need an improved and interdisciplinary approach to mitigate and understand the risks imposed by escalating environmental heat exposure.

The Icarus project will generate a psycho-physical framework for improved ability tomitigate the threats associated with increased exposure aggravated by global warming: from individual vulnerability to heat and sun exposure, to public health and collective behavior. The developed framework shall allow us to identify patterns and develop algorithms for early detection of those susceptible to becoming sick from heat and sun exposure. This may directly benefit public health as well as bridge the gap from individual to collective behavior which has relevance for policy-making and climate change mitigation. To achieve the ambitious overall aim, we have composed a consortium led by experts in thermal physiology, psychology, dermatology, pharmacological prevention of adverse effects from sunlight exposure, as well as artificial intelligence and machine learning - allowing us to complete the inter-disciplinary studies and sub-tasks.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Recruiting
        • Københavns Universitet
        • Contact:
        • Sub-Investigator:
          • Mathilde Lund, MSc
  • Greece
    • Thessaly
      • Trikala, Thessaly, Greece, 42100
        • Recruiting
        • Department of Physical Education and Sport Science
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Giorgos Gkikas, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Study Population

Healthy adult volunteers residing in Denmark (Northern Europe) or Greece (Southern Europe).

Inclusion Criteria

  • Age 18-65 years (or your protocol-specific age range)
  • Healthy as determined by medical history screening questionnaire
  • Able to provide written informed consent
  • Able to complete heat exposure and light exercise protocol
  • No heat acclimatization or extensive sun exposure in the previous 4 weeks
  • Fitzpatrick skin type I-IV (if applicable for UV testing)
  • Willing to undergo blood sampling, urine collection, and skin biopsy

Exclusion Criteria

  • History of cardiovascular, metabolic, neurological, or dermatological disease
  • History of heat-related illness (e.g., heat stroke)
  • Use of medications affecting thermoregulation or cardiovascular function
  • Smoking or substance abuse
  • Pregnancy or breastfeeding
  • Abnormal ECG or uncontrolled hypertension
  • Recent severe sunburn or UV treatment
  • Contraindications to skin biopsy
  • Inability to tolerate heat exposure during screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Standardized Heat and UV Exposure Protocol
Participants undergo a standardized 4-hour laboratory protocol to assess physiological and psychological responses to controlled heat and ultraviolet radiation exposure. The protocol includes passive heat exposure (40°C, 30% relative humidity), simulated solar UV radiation (up to 3 Standard Erythema Doses), light exercise-induced heat stress, and recovery. Core and skin temperature, cardiovascular and thermoregulatory responses, orthostatic tolerance, echocardiography, blood and urine biomarkers, skin biopsies, motor-cognitive performance, and psychological measures are assessed repeatedly. Subgroup analyses compare participants by geographic location (Denmark vs Greece) and pre-defined heat tolerance status (low vs high).
Other: Controlled Heat and Ultraviolet Radiation Exposure Protocol
Participants undergo a standardized 4-hour laboratory-based environmental exposure protocol consisting of passive heat exposure (40°C, 30% relative humidity), simulated solar ultraviolet radiation (up to 3 Standard Erythema Doses), light exercise-induced heat stress using a cycle ergometer, and recovery. Physiological, cardiovascular, thermoregulatory, biochemical, and psychological responses are assessed repeatedly throughout the protocol. The intervention is designed to quantify individual heat tolerance and combined heat-UV physiological strain under controlled conditions.
Other Names:
  • Standardized Heat Stress Protocol
  • Simulated Solar Radiation Exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Physiological Heat Tolerance
Time Frame: During 4-hour laboratory protocol
Maximum tolerable exposure time during the standardized heat and ultraviolet radiation protocol. (units of measure: Minutes)
During 4-hour laboratory protocol
Heart Rate Response
Time Frame: During 4-hour laboratory protocol
Heart rate measured continuously during heat and UV exposure to assess cardiovascular strain [unit: beats per minute (bpm)]
During 4-hour laboratory protocol

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Pressure Response
Time Frame: During 4-hour laboratory protocol
Stroke volume assessed to evaluate cardiac function during environmental stress (unit: mL/beat)
During 4-hour laboratory protocol
Cardiac Output
Time Frame: During 4-hour laboratory protocol
Ability to maintain blood pressure and consciousness during postural change following exposure (unit : L/min)
During 4-hour laboratory protocol
Orthostatic Tolerance
Time Frame: Every 60 min during the protocol
Ability to maintain blood pressure and consciousness during postural change following exposure [unit: time to presyncope (minutes)]
Every 60 min during the protocol
Echocardiographic Parameters
Time Frame: Every 60 min during the protocol
Cardiac structure and function assessed via echocardiography (ejection fraction) (unit:%)
Every 60 min during the protocol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Thessaly

Collaborators

University of Copenhagen
Bispebjerg Hospital

Investigators

  • Principal Investigator: Andreas D Flouris, PhD, 1FAME Laboratory, Department of Exercise Science, University of Thessaly, Trikala, Greece
  • Principal Investigator: Lars Nybo, PhD, Department of Nutrition, Exercise and Sports, August Krogh Building, University of Copenhagen, Copenhagen, Denmark.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2025

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

February 20, 2026

First Submitted That Met QC Criteria

March 27, 2026

First Posted (Actual)

April 3, 2026

Study Record Updates

Last Update Posted (Actual)

April 3, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03/07.02.2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hyperthermia

Clinical Trials on Controlled Heat and Ultraviolet Radiation Exposure Protocol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Taiwan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe