Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes

Sponsor

Faculdade de Motricidade Humana (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06128941

Collaborator

University of Sao Paulo (Other), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

COVID-19 has significantly impacted sports globally, with event postponements, training disruptions, and wide-ranging concerns. SARS-CoV-2 infection can result in hyperinflammation and cardiopulmonary changes, with hypoxia as an aggravating sign. Hypoxia triggers complex immunometabolic mechanisms, including activation of HIF-1α and induction of HLA-G expression. Hypoxia training protocols benefit aerobic capacity and sports performance, with potential immunological impact. Studying immunometabolic markers in this context can improve athletic preparation and athletes' general health.

Condition or Disease	Intervention/Treatment	Phase
Normobaric Hypoxia Hypoventilation Normoxia	Other: Repeated sprint	N/A

Detailed Description

Covid-19, caused by SARS-CoV-2, can progress to pulmonary hyperinflammation and cardiopulmonary changes, with hypoxia being one of the main signs of worsening. In hypoxia, there is activation of HIF-1 that induces the expression of HLA-G, an immuno-tolerogenic molecule that inhibits the hyperinflammatory response. Hypoxia training protocols can promote cardiopulmonary benefits and increase the expression of anti-inflammatory cytokines, HIF-1 and HLA-G. Immunometabolic markers have the potential to be used in the prevention, diagnosis, and treatment of diseases with inflammatory mechanisms. The objective of this study is to evaluate the influence of physical training protocols in hypoxic, normobaric, and hypobaric environments, on the immune, and metabolic response and cardiopulmonary behavior in athletes post covid-19, to identify potential biomarkers and better clarify the impact of exercise on immunometabolism post-covid-19. The study will consist of a randomized and controlled intervention, with training using different normobaric hypoxic methods; and an observational study at natural altitude (hypobaric hypoxia). In the normobaric hypoxia trial, participants will be divided into a control group that will carry out a training plan of repeated sprints in normoxia; and two other groups that will perform the same training sessions in normobaric hypoxia and with low lung volume voluntary hypoventilation. In the observational study with hypobaric hypoxia, high-performance resistance athletes will be recruited, who will comply with the training plan proposed by the team's coach at altitude. Cardiorespiratory, immunometabolic, neuromuscular, and autonomic fatigue, hematological indicators, plasma levels of lipid mediators, sHLA-G and cytokines, and the expression of HIF-1α in leukocyte cells will be evaluated. The analysis of the effect of the training methods will be carried out by ANOVA for repeated measures (parametric or non-parametric), or means comparison tests for paired samples (t or Wilcoxon) after evaluating the assumptions and the identification of associations between variables will be carried out by Binomial Logistic Regression Analysis.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Influence of Physical Training Protocols in Hypoxic, Normobaric and Hypobaric Environments, on the Immune, Metabolic Response and Cardiopulmonary Behavior in Athletes Convalescent From Covid-19

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Normobaric hypoxia (SRH) Participants will carry out training sessions in a normobaric hypoxia chamber at a simulated altitude of 3000 meters (FiO2 14.5%)	Other: Repeated sprint Duration of the study: 8 weeks of participation. Each repeated sprint training protocol: 2 training sessions per week for 4 weeks. Collection sessions: 3 collection sessions will be carried out: before the start of the training protocol - T0; at the end of the protocol, in week 4 - T1; and late, 4 weeks after the end of the protocol, in week 8 - T2. Training sessions: will be carried out on an ergometer and will consist of 3 sets of 5 sprints of 10s all-out with 20s of rest between sprints, and 5 minutes of rest between sets.
Experimental: Hypoventilation (SRH-VLH) Participants will be asked to exhale to residual functional capacity, immediately before starting each sprint, and to hold their breath until the end of the sprint	Other: Repeated sprint Duration of the study: 8 weeks of participation. Each repeated sprint training protocol: 2 training sessions per week for 4 weeks. Collection sessions: 3 collection sessions will be carried out: before the start of the training protocol - T0; at the end of the protocol, in week 4 - T1; and late, 4 weeks after the end of the protocol, in week 8 - T2. Training sessions: will be carried out on an ergometer and will consist of 3 sets of 5 sprints of 10s all-out with 20s of rest between sprints, and 5 minutes of rest between sets.
Active Comparator: Normoxia (SRN) Participants will carry out training sessions in normoxia (FiO2 20.9%)	Other: Repeated sprint Duration of the study: 8 weeks of participation. Each repeated sprint training protocol: 2 training sessions per week for 4 weeks. Collection sessions: 3 collection sessions will be carried out: before the start of the training protocol - T0; at the end of the protocol, in week 4 - T1; and late, 4 weeks after the end of the protocol, in week 8 - T2. Training sessions: will be carried out on an ergometer and will consist of 3 sets of 5 sprints of 10s all-out with 20s of rest between sprints, and 5 minutes of rest between sets.

Arm

Intervention/Treatment

Experimental: Normobaric hypoxia (SRH)

Participants will carry out training sessions in a normobaric hypoxia chamber at a simulated altitude of 3000 meters (FiO2 14.5%)

Other: Repeated sprint

Duration of the study: 8 weeks of participation. Each repeated sprint training protocol: 2 training sessions per week for 4 weeks. Collection sessions: 3 collection sessions will be carried out: before the start of the training protocol - T0; at the end of the protocol, in week 4 - T1; and late, 4 weeks after the end of the protocol, in week 8 - T2. Training sessions: will be carried out on an ergometer and will consist of 3 sets of 5 sprints of 10s all-out with 20s of rest between sprints, and 5 minutes of rest between sets.

Experimental: Hypoventilation (SRH-VLH)

Participants will be asked to exhale to residual functional capacity, immediately before starting each sprint, and to hold their breath until the end of the sprint

Other: Repeated sprint

Active Comparator: Normoxia (SRN)

Participants will carry out training sessions in normoxia (FiO2 20.9%)

Other: Repeated sprint

Outcome Measures

Primary Outcome Measures

Hypoxia Inducible Factor 1 alpha (HIF-1a) [Before, just after and 4 weeks after the training program]
Flow cytometry for PBMCs
Human Leukocyte Antigen-G (HLA-G) [Before, just after and 4 weeks after the training program]
ELISA
Cytokines (TNF-α, IL-1β, IL-6, IL-10, IL-8 and IFN-γ) [Before, just after and 4 weeks after the training program]
ELISA
Plasma levels of eicosanoids, endocannabinoids, steroid hormones, sphingolipids, ceramides and other glycerophospholipids [Before, just after and 4 weeks after the training program]
Mass Spectrometry (LC-MS/MS)
Hematological indicators (hematocrit, hemoglobin and cell count) [Before, just after and 4 weeks after the training program]
Blood count
Ventilatory thresholds and maximum oxygen consumption [Before, just after and 4 weeks after the training program]
mL/kg·min
Blood lactate concentrations [Before, just after and 4 weeks after the training program]
mmol.L-1
Muscle oximetry [Before, just after and 4 weeks after the training program]
Near-infrared spectroscopy (NIRS)
Peak force [Before, just after and 4 weeks after the training program]
Isometric mid thigh pull

Secondary Outcome Measures

Heart rate [Throughout the training program, 4 weeks]
maximum values during the training sessions (bpm)
Arterial oxygen saturation [Throughout the training program, 4 weeks]
oxymetry (%)
Subjective perception of effort [Throughout the training program, 4 weeks]
Adapted Borg scale
Blood pressure, heart rate and temperature [Before, just after and 4 weeks after the training program]
Values at rest mmHg, bpm and ºC
Anthropometric assessments and body composition [Before, just after and 4 weeks after the training program]
height (m), body mass (kg), fat free mass (kg), fat mass (kg)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

more than 5 years of training experience in an resistance modality;
participates in national or international championships regularly;
athletes convalescing from covid-19, at least 30 days after diagnosis and/or hospital discharge;
manifested mild to severe symptoms;
vaccinated or not against SARS-CoV-2;
antigen self-test for SARS-CoV-2 negative.

Exclusion Criteria:

athletes who have had an acclimatization experience or exposure to altitude lasting more than 10 days in the last 6 months;
contain signs or symptoms of acute covid-19;
present a positive SARS-CoV-2 antigen self-test;
pregnant or postpartum women;
use anti-inflammatory or immunosuppressive medications.