Acute Health Effects of High Temperature Exposure

Acute Health Effects of High Temperature Exposure in Healthy Young Adults: a Randomized Controlled Study

This is a randomized controlled human exposure crossover study. Investigators aims to assess the acute effects of high temperature exposure and the underlying mechanisms.

Study Overview

• Status: Active, not recruiting
• Conditions: Cognitive Function; Cardiovascular System; Respiratory System
• Intervention / Treatment: Other: high temperature (32℃) group; Other: moderate temperature (22℃) group

Detailed Description

The investigators will conduct a randomized controlled human exposure crossover study among about 30 healthy young adults in Shanghai, China. Each subject will be exposed twice: once to the high temperature (32℃) and once to moderate temperature (22℃) in a chamber for about 2 hours. During the exposure session, each subject will be requested to rest. Health examinations will be conducted immediately prior to exposure, during the period of exposure and after exposure. Health examinations include symptom questionnaire, blood pressure tests, cognitive function tests, magnetic resonance imaging, skin tests, spirometry, and Holter monitoring. Investigators plan to collect blood, urine and oropharyngeal swabs samples.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of Environmental Health, School of Public Health, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Living in Shanghai during the study period;
• Body mass index > 18.5 and ≤ 28;
• right-handed;
• receiving or having received higher education;
• with ability to read and understand Chinese smoothly.

Exclusion Criteria:

• Smoking and alcohol abuse;
• Current drug and dietary supplements intake;
• Subjects with allergic diseases, such as allergic rhinitis, allergic asthma, and atopy;
• Subjects with cardiovascular diseases, such as congenital heart disease, pulmonary heart disease, and hypertension;
• Subjects with respiratory diseases, such as asthma, chronic bronchitis, and chronic obstructive pulmonary disease;
• Subjects with chronic diseases, such as diabetes, chronic hepatitis, and kidney disease;
• Subjects who have a history of major surgery due to the cardiovascular, cerebrovascular, respiratory, or neurological diseases;
• Subjects with neurologic disorders, such as stroke, traumatic brain injury, epilepsy, and schizophrenia;
• Abnormal spirometry (FEV1 and FVC ≤ 75% of predicted and FEV1/FVC ≤ 0.65);
• Subjects with color vision disabilities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: high temperature (32℃) group; Subjects in exposure group will be exposed to high temperature (32℃) for about 2 hours in a chamber.	Other: high temperature (32℃) group; The exposure group will be exposed to high temperature (32℃) in a chamber for about 2 hours, resting during the whole periods.
Sham Comparator: moderate temperature (22℃) group; Subjects in exposure group will be exposed to moderate temperature (22℃) for about 2 hours in a chamber.	Other: moderate temperature (22℃) group; The exposure group will be exposed to thermoneutral temperature (22℃) in a chamber for about 2 hours, resting during the whole periods.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Results of Stroop Tests	Investigators plan to measure the changes of cognitive function using Stroop Test. The time taken to complete the test could reflect cognitive function, and a shorter time means better cognitive function.	The tests will be conducted before exposure and immediately after the exposure session
Changes of forced expiratory volume in the first second (FEV1)	Investigators plan to measure the changes of the forced expiratory volume in 1 s (FEV1) using a smart spirometer (Model A1, BreathHome, China) supervised by professional medical staff. Before the pulmonary function test, subjects will practice several times by themselves. During the examination, each subject stands and clamps the nose clip, and repeats the test, with the best result as the criterion. FEV1 reflect pulmonary function.	The tests will be examined before exposure and half an hour after exposure
Changes of forced vital capacity (FVC)	Investigators plan to measure the changes of forced vital capacity (FVC) using spirometer (Model A1, BreathHome, China). FVC reflects the expiratory resistance of large airways.	FVC will be examined before exposure and half an hour after exposure
Changes of peak expiratory flow rate (PEF)	Investigators plan to measure the changes of peak expiratory flow (PEF) using smart spirometer (Model A1, BreathHome, China). PEF reflects airway patency and respiratory muscle strength.	FVC will be examined before exposure and half an hour after exposure
Changes of maximum expiratory flow rate at 25% vital capacity (MEF25)	Investigators plan to measure the changes of maximum expiratory flow rate at 25% vital capacity. MEF25% reflects the early stage of expiratory flow rate.	MEF25 will be examined before exposure and half an hour after exposure
Changes of maximum expiratory flow rate at 50% vital capacity (MEF50)	Investigators plan to measure the changes of maximum expiratory flow rate at 50% vital capacity using smart spirometer (Model A1, BreathHome, China). MEF50 reflects the interim stage of expiratory flow rate.	MEF50 will be examined before exposure and half an hour after exposure
Changes of maximum expiratory flow rate at 75% vital capacity (MEF75)	Investigators plan to measure the changes of maximum expiratory flow rate at 50% vital capacity (MEF75%) using smart spirometer (Model A1, BreathHome, China). MEF75 reflects the terminal stage of expiratory flow rate.	MEF75 will be examined before exposure and half an hour after exposure
Changes of pulse wave velocity measured by an arteriography device performing oscillometric measurement	Pulse wave velocity (PWV) is one of the arterial stiffness indicators. The changes of PWV will be measured.	Pulse wave velocity will be examined before exposure and immediately after the exposure session
Changes of AIx@75 measured by an arteriography device performing oscillometric measurement	Augmentation index normalized to 75 bpm heart rate (AIx@75) is one of the arterial stiffness indicators. The changes of AIx@75 will be measured.	AIx@75 will be examined before exposure and immediately after the exposure session
Changes of reflection magnitude measured by an arteriography device performing oscillometric measurement	Reflection magnitude is one of the arterial stiffness indicators. The changes of reflection magnitude will be measured.	Reflection magnitude will be examined before exposure and immediately after the exposure session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	The changes of systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured.	Blood pressure will be examined before exposure and immediately after the exposure session
Results of Schulte table Tests	Investigators plan to measure the changes of cognitive function using Schulte table. The time taken to complete the test and the accuracy could reflect cognitive function. Less time and greater accuracy mean better cognitive function.	The tests will be conducted before exposure and immediately after the exposure session
Activated brain regions demonstrating neural activity related to the high temperature exposure	Investigators plan to measure brain activity associated with high temperature exposure by magnetic resonance imaging (MRI). Brain imaging data will be extracted from MRI data. The fractional amplitude of low frequency fluctuation (fALFF) would be extracted to reflect neural activity of brain regions.	1 hour after exposure session
Activated brain regions demonstrating neural connectivity related to the high temperature exposure	Investigators plan to measure brain activity associated with high temperature exposure by magnetic resonance imaging (MRI). Brain imaging data will be extracted from MRI data. The degree of centrality (DC) would be extracted to reflect neural connectivity of brain regions.	1 hour after exposure session
Activated brain regions demonstrating neural synchronization related to the high temperature exposure	Investigators plan to measure brain activity associated with high temperature exposure by magnetic resonance imaging (MRI). Brain imaging data will be extracted from MRI data. The regional homogeneity (ReHo) would be extracted to reflect neural synchronization of brain regions.	1 hour after exposure session
Changes of airway inflammation indicator fractional concentration of carbon monoxide (FeCO)	Investigators plan to measure the changes of fractional concentration of carbon monoxide.	FeCO will be examined before exposure and half an hour after exposure
Changes of airway inflammation indicator fractional exhaled nitric oxide (FeNO)	Investigators plan to measure the changes of fractional exhaled nitric oxide.	FeNO will be examined before exposure and half an hour after exposure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in metabolic profiling detected in blood between the two exposures	The differential metabolic profiling in blood related to high temperature exposure will be detected by mass spectrometry-based non-targeted metabolomics.	1 hour after the exposure session
Differences in protein levels detected in blood between the two exposures	The differentially expressed proteins in blood related to high temperature exposure will be detected by non-targeted proteomics.	1 hour after the exposure session
Change in C reactive protein (CRP) concentrations	Change in the concentrations of C reactive protein in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Changes of the scores of thermal sensation questionnaires	Changes of scores of thermal sensation questionnaires which ranged from -5 to 5. Zero score refers to the thermal comfort sensation. Higher scores refer to more uncomfortable sensations of hot. Lower scores refer to more uncomfortable sensations of cold.	before exposure and immediately after the exposure session
Differences in RNA expression levels detected in serum transcriptomics between the two exposures	Illumina-based transcriptomics is non-targeted. The study is to find the differentially expressed exosome RNA in serum after high temperature exposure	1 hour after the exposure session
Differences in protein levels detected in blood Clara cell protein (CC16) between the two exposures	Investigators plan to measure the changes of Clara cell protein using enzyme linked immunosorbent assay (ELISA). Clara cell protein (CC16) indicate lung epithelial injury.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Differences in protein levels detected in blood chitinase-3-like protein 1 (YKL-40) between the two exposures	Investigators plan to measure the changes of chitinase-3-like protein 1 protein using enzyme linked immunosorbent assay (ELISA). YKL-40 represents airway inflammation and remodeling.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Changes of heart rate variability (HRV) parameter RMSSD	Investigators plan to measure the changes of HRV parameter the root mean square of successive differences between adjacent normal cycles (RMSSD) .	Volunteers will be asked to wear electrographic Holter monitors for 24 hours from 1:00 P.M. at the day of intervention to 1:00 P.M. at the next day.
Changes of heart rate variability (HRV) parameter SDNN	Investigators plan to measure the changes of heart rate variability parameter standard deviation of NN intervals (SDNN) .	Volunteers will be asked to wear electrographic Holter monitors for 24 hours from 1:00 P.M. at the day of intervention to 1:00 P.M. at the next day.
Changes of heart rate variability (HRV) parameter PNN50	Investigators plan to measure the changes of heart rate variability parameter percent of NN50 in the total number of NN intervals (PNN50).	Volunteers will be asked to wear electrographic Holter monitors for 24 hours from 1:00 P.M. at the day of intervention to 1:00 P.M. at the next day.
Differences in DNA methylation levels detected in whole-blood between the two exposures	Genome-wide DNA methylation in whole-blood were detected using Illumina 935K Beadchip. The study is to identify differential CpG loci after high temperature exposure.	1 hour after the exposure session
Change in tumor necrosis factor-α (TNF-α) concentrations	Change in the concentrations of TNF-α in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in oxidized low density lipoprotein (Ox-LDL) concentrations	Change in the concentrations of Ox-LDL in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in malondialdehyde (MDA) concentrations	Change in the concentrations of MDA in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in von Willebrand factor (vWF) concentrations	Change in the concentrations of vWF in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in fibrinogen concentrations	Change in the concentrations of fibrinogen in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in endothelial nitric oxide synthase (eNOS) concentrations	Change in the concentrations of eNOS in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in endothelin-1 (ET-1) concentrations	Change in the concentrations of ET-1 in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in blood glucose concentrations	Change in the concentrations of blood glucose.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in insulin concentrations	Change in the concentrations of insulin in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in low-density lipoprotein cholesterol (LDL) concentrations	Change in the concentrations of LDL in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in total cholesterol (TC) concentrations	Change in the concentrations of TC in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in apolipoprotein B (ApoB) concentrations	Change in the concentrations of ApoB in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in matrix metallopeptidase 2 (MMP2) concentrations	Change in the concentrations of MMP2 in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in matrix metallopeptidase 9 (MMP9) concentrations	Change in the concentrations of MMP9 in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Changes of skin sebum level	Evaluation of the differential sebum level between the two groups	60 minutes and 120 minutes of exposure.
Changes of facial secreted sebum composition	Evaluation of the differential facial secreted sebum composition between the two groups	One hour after the exposure session
Changes of the luminosity on the cheeks	Evaluation of the differential facial luminosity between the two groups. The luminosity on the cheeks of the participants were visually assessed by the dermatologist with the naked eyes. The skin luminosity was rated on a 4-point scale (0 to 3, with larger scores indicating more glossy).	before exposure and at 40 minutes after the end of exposure
Changes of the pores on the cheeks	Evaluation of the differential pores sizes between the two groups. The pores on the cheeks of the participants were visually assessed by the dermatologist with the naked eyes. The pore appearance was rated on a 6-point scale (0 to 5, with larger scores indicating larger pore size).	before exposure and at 40 minutes after the end of exposure
Changes of subjective skin sensations	Evaluation of the differential subjective skin sensations between the two groups. The questionnaire consisted of seven questions regarding dryness, oiliness, stickiness, tightening, itchiness, tingling, and freshness. Each participant was asked to self-evaluate their skin sensations on a 4-point scale from 0 to 3, indicating "not at all", "somewhat", "fairly", and "fully compliant".	30, 60, 90, and 120 minutes after the start of each exposure session
Changes of stratum corneum protein levels	Evaluation of the differential stratum corneum (SC) protein levels between the two groups	within 30 minutes after the end of exposure
Differences in lipid metabolites levels detected in skin surface between the two exposures	The differentially lipid metabolites levels in skin surface related to high temperature exposure will be detected by targeted quantitative lipidomic analysis.	Skin surface sebum was collected 5 minutes after exposure
Change in total antioxidant capacity of collected stratum corneum	Change of the total antioxidant capacity in collected stratum corneum will be measured.	within 30 minutes after the end of exposure
Change in kallikrein-5 concentrations of collected stratum corneum	Change of the concentrations of kallikrein-5 in collected stratum corneum will be measured.	within 30 minutes after the end of exposure
Change in interleukin-1α concentrations of collected stratum corneum	Change of the concentrations of interleukin-1α in collected stratum corneum will be measured.	within 30 minutes after the end of exposure
Change in total protein concentrations of collected stratum corneum	Change of the concentrations of total protein in collected stratum corneum will be measured.	within 30 minutes after the end of exposure
Change in interleukin-1 receptor antagonist concentrations of collected stratum corneum	Change of the concentrations interleukin-1 receptor antagonist in collected stratum corneum will be measured.	within 30 minutes after the end of exposure
Differences in protein levels related to cardiovascular system and inflammation detected in blood between the two exposures	The differentially expressed proteins in blood related to cardiovascular system and inflammation after high temperature exposure will be detected by targeted Olink proteomics.	1 hour after the exposure session
Change in brain-derived neurotrophic factor (BDNF) concentrations	Change in the concentrations of BDNF in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in glial cell line-derived neurotrophic factor (GDNF) concentrations	Change in the concentrations of GDNF in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in Gamma-aminobutyric acid (GABA) concentrations	Change in the concentrations of GABA in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in glutathione (GSH) concentrations	Change in the concentrations of IFN in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session
Change in interferon (IFN) concentrations	Change in the concentrations of IFN in blood.	1:00 P.M. on the day of the exposure session, 1 hour after the exposure session

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Study Director: Haidong Kan, PhD, Department of Environmental Health, School of Public Health, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2022
• Primary Completion (Actual): November 19, 2022
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 28, 2022
• First Submitted That Met QC Criteria: October 8, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Randomized controlled trial; cognitive function; High Temperature; Cardiovascular effects
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: FDUEH-8

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
• product manufactured in and exported from the U.S.: No