Direct and Cross Effects of Adaptation to Systemic Hyperthermia: Impact on Quality of Life, Neurohormonal and Psychophysiological Human Status

Quality of Life Clinical Trial

Official title:

Direct and Cross Effects of Adaptation to Systemic Hyperthermia: Impact on Quality of Life, Neurohormonal and Psychophysiological Human Status

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04089410
• Other study ID #: ????-?19-119012190093-4
• Status: Completed
• Phase: N/A
• Start date: January 14, 2019
• Est. completion date: December 27, 2019

Study information

• Verified date: November 2020
• Source: I.M. Sechenov First Moscow State Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Life expectancy and quality of human life are important indicator of the sustainable development of the society. At the same time, the physical, functional, emotional and psychological components of the of the quality of life evaluation are subjected to be evaluated objectively and corrected using modern medical and socio-psychological methods. According to a fair number of experts, the arsenal of means for functional rehabilitation and health promotion is limited, and its expansion is only possible on the basis of the principles of adaptation medicine and their translation from experimental research into specific preventive and health-promoting technologies. The study is aimed at the development in molecular-endocrine, neuro-visceral and psychophysiological complex mechanisms of human long-term adaptation to systemic modern heating device-based hyperthermia for the development of medical technology focused on optimization in physical functioning, neuro-autonomic regulation, psycho-emotional status and stress- resistance as objective characteristics of humans' quality of life in working age. The novelty of the project is the disclosure of key mechanisms of adaptational direct and cross-effects to the prolonged systemic individually dosed hyperthermia underlying the optimization of stress-resistance, psycho-physiological status and exercise tolerance of practically healthy persons and leading to an increase in the subjectively perceived quality of life. The discovery of the mechanisms of hyperthermically induced neuroplasticity (in terms of the dynamics of oxidative stress, heat shock proteins and the brain derived neurotrophic factor) will also have a scientific significance, which in the long term prospectives may play a role in the development of technics for the prevention and rehabilitation of age-associated neuro-degenerative processes and diseases.

Description:

Hyperthermic Fitness Treatment (HFT) is proved in many applied and clinical trials to be a helpful tool for enhancing thermal acclimation, physical tolerance and endurance, improving cardiovascular dysfunctions, normalizing metabolic status and body weight in patients with chronic non-infectious diseases and in aged healthy individuals. Clinical effects of hyperthermia acclimation or repeated sauna's sessions were investigated in series of well-designed placebo-controlled studies at different cohorts of Bronchial Asthma (BA), Chronic Obstructive Pulmonary Disease (COPD), Cardiovascular Disease (CVD) Metabolic Syndrome and Obesity (MS-O) patients, qualified professional sportsmen and healthy volunteers. Effects of sauna bathing and hyperthermic treatments (acclimation to systemic, whole body dosed hyperthermia, which leads to core temperature increase on 2,0-2,5oC) are accurately described in well-controlled medical studies, performed by experienced researchers imposing different protocols (from 1 session lasting 15-20 min, daily 1 week up to 2 sessions per day, 3 weeks). The generalized result of the most trials suggests adaptation to hyperthermia (sauna bathing sessions) is accompanied by a multi-faceted molecular, cellular, organic and systemic, organismic responses - by progressively increased resistance to thermal stressors, increased bronchial conductivity and pulmonary ventilation, sweating; stimulated activation of neuro-humoral and cardiovascular systems, boosted microcirculation and, as a consequence, providing more efficient transport and utilization of O2 by body tissues, resulting in increase of exercise tolerance, physical activity, normalization of appetite, balancing thermogenesis and heat release. Mechanisms underlying the described clinical effects are partially connected with increased production of some neurotransmitters, hormones and peptides, among them - Brain derived neurotropic factor (BDNF), Somatotropin (Human Growth Hormone - HGH), Heat Shock Proteins family as cell signaling pathways inducers etc. In spite of difference in study design, protocols, and hyperthermic mashines - devices, it is safe to make the conclusion that periodic individually adapted hyperthermic sessions are capable to induce haematological, neuro-humoral, cardiorespiratory and antioxidant adaptation to provide pathogenetic treatment and rehabilitation of patients with chronic non-infectious diseases. Enhanced stress resistance and improved oxygen transfer/utilization are basic mechanisms whereby the organism increases its resistance to any physical and environmental stressors and to variety of pathogenic factors. The described Hyperthermic Fitness Treatment (HFT) method is safe, has no significant complications or adverse side effects and is generally very well tolerated by sportsmen, healthy persons and different clinical patients' groups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: December 27, 2019
• Est. primary completion date: December 9, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 30 Years

Eligibility

Inclusion Criteria:

• Outpatients, young healthy volunteers
• Age > 19 years (20 - 30)
• Gender: male
• Healthy state (no chronic noninfectious diseases, documented by medical check-up results, obtained in 1-2 months before, not later), mobility (absence of orthopedic problems), satisfactory level of fitness
• Ability to perform activities of daily living
• Ability to attend all treatments and clinical-laboratory measurements
• Signed informed consent form

Exclusion Criteria:

• Infectious diseases
• Increased body temperature before any step of the study
• Individual hyperthermia (sauna) intolerance
• Any condition which in the opinion of the investigator would make it unsafe or unsuitable for the volunteer to participate in this study e.g. expected survival <1 year
• Participation in another clinical study with an investigational product within 28 days prior to enrolment or previous randomization to an investigational product in another ongoing clinical study

Related Conditions & MeSH terms

• Altitude Sickness
• Exercise Tolerance
• Fever
• Hypoxia
• Hypoxia, Altitude
• Metabolic Disturbance
• Quality of Life

Intervention

Device:
• Hyperthermic Fitness Treatment (HFT)
The Hyperthermic Fitness Treatment uses Alfa Basic capsule, an ergonomic camera in which a participant may take a lying position and undergo hyperthermia procedures (infrared heating with intracapsule temperature increase up to 80 degrees C?), the head being outside the camera blown by cool air with a built-in ventilator. HFT is comparable to dry sauna bathing. Core body temperatures will be raised to 37.5-38.5°C?. Recommended duration of one HFT session is 40 min. All the HFT group participants while undergoing sessions in the Cocoon will be dressed in bathing suits.
• Placebo Hyperthermic Fitness Treatment
Attenuated heating with less heat set (20-30 degrees C?). This results in no increase of core body temperature. The participant will still feel heat and will see similar lighting and hear similar sounds as those occurring during actual HFT, and will be in the capsule for the same period of time.

Other:
• Physical Examination
Resting hearth rate (HR), Systolic and Diastolic blood pressure (SBP and DBP) values are measured twice in supine position using an automatic tonometer after 5 min of rest. Body mass (BM) and height are measured to calculate Body Mass Index. Body composition is assessed with the use of portable body-impedance-meter for the whole body impedance-analysis. Body core temperature, Blood pressure (BP) and Heart rate (HR) are measured before and right after each session. Arterial oxygen saturation (SpO2) and HR is monitored continuously by the use of a pulse oximeter, attached to the index fingertip of non dominant hand.
• Assessment of Cardiorespiratory Fitness
An assessment of exercise tolerance and cardiorespiratory fitness (ET, CRF) is carried out with the use of Cardiopulmonary Exercise Test - CPET). Testing is carried out using a gas analyzer and an Intertrack treadmill. Evaluation of gas exchange parameters conducted according to a given program - Cardiopulmonary load testing.
• Autonomic Balance, Orthostatic and Hypoxic tolerance
Evaluation of Autonomic balance is assesed using Heart Rate Variability (HRV) analysis. The HRV test relies on a 5-min RR interval (time in milliseconds between two R waves of the electrocardiogram complex) recorded at rest for 5 min supine (SU) followed of 5 min resting time. Measurement of the interval duration between two R waves of the cardiac electrical activity are performed with a HR monitor. Orthostatic tolerance is assessed after ANS balance assessment by HRV analysis to continue RR intervals registration for 3 min after participant was asked to stand up taking a vertical position near the couch. The individual sensitivity to hypoxia is determined by conducting a 10-minute hypoxic test (HT) - breathing through a facial mask by a gas mixture with 11% of O2, with minute-by-minute monitoring of HR and hemoglobin saturation by oxygen (SaO2). Arterial blood pressure is recorded before and after HT.
• Psychological Testing
Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), which is a self-completed quantity of health-related QoL. Participants are asked to complete the Pittsburgh Sleep Quality Index (PSQI), a retrospective self-report measure assessing their quality of sleep during the last three weeks preceding the study. Anxiety level is estimated by using State and Trait Anxiety Scales (SA and TA) developed by Ch. Spielberger Subjective Ratings of Thermosensation and Pain.Participants rate their comfort, thermosensation, and pain by fixing results in visual-analogous scale (VAS) while passing each of HFT treatment.
• Measurement of Blood Markers
Periferal venous blood (10 ml) sumples of the fastest (overnight fast) study subjects are withdrawn by a qualified laboratory technician via aseptic technique from the antecubital vein in the sitting position, using sterile needles and are collected. Serum BDNF, HGH, HSPs (60, 70, 90) concentrations are determined.

Locations

Country	Name	City	State
Russian Federation	Students health and quality of life laboratory	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

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* Note: There are 74 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cardiopulmonary Exercise Test	An assessment of exercise tolerance and cardiorespiratory fitness (ET, CRF) is carried out by Cardiopulmonary Exercise Test - CPET) with the use of Fitmate MED gas analyzer (COSMED, Italy) and an Intertrack treadmill (Shiller, Switzerland).	Week 1
Primary	Change in Cardiopulmonary Exercise Test	An assessment of exercise tolerance and cardiorespiratory fitness (ET, CRF) is carried out by Cardiopulmonary Exercise Test - CPET) with the use of Fitmate MED gas analyzer (COSMED, Italy) and an Intertrack treadmill (Shiller, Switzerland).	Week 5
Primary	Change in Cardiopulmonary Exercise Test	An assessment of exercise tolerance and cardiorespiratory fitness (ET, CRF) is carried out by Cardiopulmonary Exercise Test - CPET) with the use of Fitmate MED gas analyzer (COSMED, Italy) and an Intertrack treadmill (Shiller, Switzerland).	Week 13
Primary	Measurement of Blood Markers	Serum BDNF, HGH, HSPs (60, 70, 90), Irisin concentrations	Week 1
Primary	Measurement of Blood Markers	Serum BDNF, HGH, HSPs (60, 70, 90), Irisin concentrations	Week 5
Primary	Measurement of Blood Markers	Serum BDNF, HGH, HSPs (60, 70, 90), Irisin concentrations	Week 13
Primary	Psychological stress tolerance: Quality of Life	We assessed QoL using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), which is a self-completed quantity of health-related QoL. This questionnaire comprises eight domains covering physical functioning, vitality, role-physical, social functioning, bodily pain, role-emotional, general health and mental health. A high score indicates a better QoL characteristic. Furthermore, there are two summary scores which summarize two domains: first the Mental Component Summary and second the Physical Component Summary.	Week 1
Primary	Psychological stress tolerance: Quality of Life	We assessed QoL using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), which is a self-completed quantity of health-related QoL. This questionnaire comprises eight domains covering physical functioning, vitality, role-physical, social functioning, bodily pain, role-emotional, general health and mental health. A high score indicates a better QoL characteristic. Furthermore, there are two summary scores which summarize two domains: first the Mental Component Summary and second the Physical Component Summary.	Week 5
Primary	Psychological stress tolerance: Quality of Life	We assessed QoL using the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), which is a self-completed quantity of health-related QoL. This questionnaire comprises eight domains covering physical functioning, vitality, role-physical, social functioning, bodily pain, role-emotional, general health and mental health. A high score indicates a better QoL characteristic. Furthermore, there are two summary scores which summarize two domains: first the Mental Component Summary and second the Physical Component Summary.	Week 13
Primary	Psychological stress tolerance: Sleep Quality	Assessment of Sleep Quality(The Pittsburgh Sleep Quality Index)	Week 1
Primary	Psychological stress tolerance: Sleep Quality	Assessment of Sleep Quality(The Pittsburgh Sleep Quality Index)	Week 5
Primary	Psychological stress tolerance: Sleep Quality	Assessment of Sleep Quality(The Pittsburgh Sleep Quality Index)	Week 13
Primary	Psychological stress tolerance: Anxiety level	Assessment of Anxiety level (State and Trait Anxiety Scales developed by Ch. Spielberger)	Week 1
Primary	Psychological stress tolerance: Anxiety level	Assessment of Anxiety level (State and Trait Anxiety Scales developed by Ch. Spielberger)	Week 5
Primary	Psychological stress tolerance: Anxiety level	Assessment of Anxiety level (State and Trait Anxiety Scales developed by Ch. Spielberger)	Week 13
Secondary	Hearth rate	Resting hearth rate (HR) values are measured twice in supine position.	Up to week 13
Secondary	Blood pressure	Systolic and Diastolic blood pressure (SBP and DBP) values are measured twice in supine position.	Up to week 13
Secondary	Body Mass Index	Body mass (BM) in kilograms and height in meters are measured (Seca 888 scale, Hamburg, Germany) to calculate Body Mass Index (BMI, in kg/m2). Metabolic rate at rest is measured in supine position by Fitmate MED gas analyzer (COSMED, Italy).	Change between baseline and week 13
Secondary	Metabolic rate	Metabolic rate at rest is measured in supine position by Fitmate MED gas analyzer (COSMED, Italy).	Change between baseline and week 13
Secondary	Body mass	Body mass is measured in kilograms	Up to week 13
Secondary	Height	Height is measured in meters	1 week
Secondary	Autonomic Balance, Orthostatic and Hypoxic tolerance.	For the assessment of participants' autonomic regulation Heart Rate Variability (HRV) analysis is selected.Briefly, the HRV test relied on a 5-min RR interval (time in milliseconds between two R waves of the electrocardiogram complex) recorded at rest for 5 min supine (SU) followed of 5 min resting time. Measurement of the interval duration between two R waves of the cardiac electrical activity is performed with a HR monitor (VNS-Spectrum hardware and software complex (Neurosoft Company, Ivanovo, Russia).	Change between baseline and week 13

External Links

•   Brenner I.K. et al. The impact of heat exposure and repeated exercise on circulating stress hormones. European Journal of Applied Physiology and Occupational Physiology.1997; 76(5): 445-454
•   Brigadski T., and Leßmann V. BDNF: a regulator of learning and memory processes with clinical potential. e-Neuroforum 2014; 5, 1-11. doi: 10.1007/s13295- 014- 0053- 9
•   Brisson G., Boisvert P., Peronnet F., Quirion A., Senecal L. Face cooling-induced reduction of plasma prolactin response to exercise as part of an integrated response to thermal stress. Eur J Appl Physiol Occup Physiol 1989; 58: 816-820
•   Campbell B., Zito G., Colquhoun R., Martinez N., St Louis C. et al. Inter- and intra-day test-retest reliability of the Cosmed FitmateProTM indirect calorimeter for resting metabolic rate. Kathryn Raines University of South Florida, Tampa, Florida, US
•   Halcox Julian P.J., Deanfield John, Shamaei-Tousi Alireza, Henderson Brian, Steptoe Andrew, Coates Anthony R.M., Singhal Atul and Lucas Alan. Circulating Human Heat Shock Protein 60 in the Blood of Healthy Teenagers: A Novel Determinant of Endothelial
•   Reyes Del Paso G.A., Langewitz W., Mulder L.J., Van Roon A., Duschek S. The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: A review with emphasis on a reanalysis of previous studies. Psychophysiology 2013; 50: