OXY-SPORT: Enriched Oxygen Mixtures in Athletes

Sponsor

University of Padova (Other)

Overall Status

Completed

CT.gov ID

NCT04366427

Collaborator

Performa di Crocicchia Srl (Other)

Enrollment

Location

Arms

3.5

Actual Duration (Months)

11.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Currently, Hyperbaric Oxigen (HBO) is a widely used treatment for several conditions. There are 14 indications for HBO, officially recognized by the Undersea and Hyperbaric Medical Society (UHMS), but research is discovering other interesting applications.

HBO plays an important role in enhancing antioxidant defense mechanisms by increasing radical oxygen species (ROS) and nitric oxide species (NOS). This controlled oxidative stress has been shown to stop the vicious circle of inflammation - damage - hypoxia already seen in several diseases. Increased neoangiogenesis has been demonstrated at pressures of 2 atmospheres absolute (ATA), while effects helping ischemic tissues need pressures between 2.5 and 2.8 ATA to develop. Also, stem cell proliferation and mobilization have been demonstrated after HBO treatments.

During sports activities, metabolism generates waste products - mostly CO2, lactic acid, but also ROS. HBO could be useful in modulating antioxidant mechanisms and increasing stem cell mobilization, thus helping cells in the recovery after training and sportive competitions.

The authors hypothesize that:

HBO can reduce oxidative stress and induce stem cell mobilization in healthy professional athletes;
hyperoxic mixtures can reduce oxidative stress and induce stem cells mobilization in healthy professional athletes;
HBO at low pressures (L-HBO at 1.45 ATA) is at least comparable to conventional HBO (at 2.5 ATA) in reducing oxidative stress and increasing stem cell mobilization.

The Authors will include healthy athletes. These will be randomly assigned to a control group, a L-HBO group, a HBO group, a 30% O2 group, or a 50% O2 group.

The Authors will assess oxidative stress changes and stem cells proliferation before and after 20 L-HBO/HBO/30% O2 mix/50% O2 mix treatments, and after 2 months after the end of treatments.

Condition or Disease	Intervention/Treatment	Phase
Oxidative Stress Stem Cell Research	Combination Product: L-HBO Combination Product: HBO Combination Product: 30% O2 Combination Product: 50% O2	Phase 2

Detailed Description

Subjects will be recruited through public announcements in local gyms and gathered to explain the protocol. Those willing to participate will sign a written informed consent and recruited. To be included, all the subjects will undergo a general medical screening to allow hyperbaric treatments. This will include weight, height, non-invasive arterial blood pressure, and heart rate measurements.

After inclusion, subjects will be randomly assigned to three arms using an electronic number generator by personnel not directly involved in the experiment:

Arm 1(control): no intervention.
Arm 2 (L-HBO): treated with oxygen at 1.45 ATA for 60 min (inclusive of compression and decompression times, and an air break of 3 minutes breathing air);
Arm 3 (HBO): treated with oxygen at 2.5 ATA for 60 min (inclusive of compression and decompression times, and an air break of 3 minutes breathing air).
Arm 4 (30% O2): breathing an air mixture with 30% of oxygen at atmospheric pressure (1 ATA).
Arm 5 (50% O2): breathing an air mixture with 50% of oxygen at atmospheric pressure (1 ATA).

Subjects included in Arm 2, 3, 4, 5 will undergo a total of 20 treatments. They will follow a personalized diet proportional to their energetic expenditure.

The Authors will identify 3 time-points in the protocol:

TIME 0 (T0): immediately after inclusion, before any treatment or experiment; TIME 1 (T1): at the end of HBO treatments; TIME 2 (T2): 2 months after the end of HBO treatments.

The following exams will be performed on the included subjects:

a standardized panel including Complete Blood Count (CBC), creatinine, Blood Urea Nitrogen (BUN), C reactive protein, and VES will be performed at T0, T1, and T2.
oxidative stress markers will be analyzed on blood, urine, and saliva samples. On blood samples (T0; T1; T2), the Authors will measure IL-1 beta, IL-6, TNF-alfa, reactive oxygen species and total antioxidant capacity (by paramagnetic resonance), total (tot) and reduced (red) aminothiols (by fluorescence spectroscopy), 3-nitrotyrosine (3-NT) (by competitive immunoassay).

On urine samples (T0; T1; T2), the Authors will assess lipid peroxidation by measuring 8-isoprostane concentration (by competitive immunoassay), nitrite and nitrate (NO2/NO3) concentration (by colorimetry based on the Griess reaction), inducible Nitric Oxide Synthase (by ELISA commercially available kit), creatinine, neopterine, and uric acid concentrations, 8-oh-2-deoxyguanosine (by competitive immunoassay).

On saliva samples (T0; T1; T2) the Authors will measure reactive oxygen species and total antioxidant capacity (by paramagnetic resonance), and cortisol (by competitive immunoassay).

stem cells will be analyzed on blood samples (at T0, T1, T2) (by flow cytometry).

Blood samples (approximately 6-12 ml) will be drawn from the veins of the forearms (preferentially on the non-dominant limb); plasma and erythrocytes will be separated by centrifuge at 1000×g for 10 min at 4°C. Urine samples will be collected by voluntary voiding in sterile containers. 1 mL of saliva will be obtained by Salivette devices (Sarstedt, Nümbrecht, Germany). The subjects will be instructed to refrain from drinking, eating, smoking, brushing their teeth, and using mouthwash in the 30 min before salivary collection.

All samples will be stored in multiple aliquots at - 80 °C until assayed and thawed only once before analysis.

With this setting, blinding of patients and investigators will be impossible due to different structural characteristics. However, outcome assessors will be blinded to patients' allocation.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Five arms: one control without treatment; one at low pressure (1.45 ATA); one at standard pressure (2.5 ATA); one at atmospheric pressure (1 ATA) breathing air mixture with 30% O2; one at atmospheric pressure (1 ATA) breathing air mixture with 50% O2;Five arms: one control without treatment; one at low pressure (1.45 ATA); one at standard pressure (2.5 ATA); one at atmospheric pressure (1 ATA) breathing air mixture with 30% O2; one at atmospheric pressure (1 ATA) breathing air mixture with 50% O2;

Masking:

Single (Outcomes Assessor)

Masking Description:

Participants, Care Provider, and Investigators will not be masked. Only outcome assessors will only evaluate data without knowing the arm the patients were assigned to.

Primary Purpose:

Treatment

Official Title:

Effects of Enriched Oxygen Mixtures and Exercise on Oxidative Stress and Stem Cells Proliferation in Athletes.

Actual Study Start Date :

Sep 15, 2020

Actual Primary Completion Date :

Nov 15, 2020

Actual Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-pressure hyperbaric oxygenation (L-HBO) Low-pressure hyperbaric oxygen administration at 1.45 ATA for 60 minutes, inclusive of compression and decompression times, and a 3-minute air pause at the midtime. For a total of 20 sessions (3-4 per week).	Combination Product: L-HBO as previously described. Other Names: Low Pressure Oxygenation
Experimental: Standard-pressure hyperbaric oxygenation (HBO) Standard pressure hyperbaric oxygen administration at 2.5 ATA for 60 minutes, inclusive of compression and decompression times, and a 3-minute air pause at the midtime. For a total of 20 non-consecutive sessions (3-4 per week).	Combination Product: HBO as previously described. Other Names: Standard Pressure Oxygenation
No Intervention: Control Control group of athletes, no intervention.
Experimental: 30% O2 Administration of air mixture with 30% O2, subjects breathing this mixture for 60 minutes for a total of 20 non-consecutive sessions (3-4 per week).	Combination Product: 30% O2 as previously described Other Names: 30% O2 mixture
Experimental: 50% O2 Administration of air mixture with 50% O2, subjects breathing this mixture for 60 minutes for a total of 20 non-consecutive sessions (3-4 per week).	Combination Product: 50% O2 as previously described Other Names: 50% O2 mixture

Outcome Measures

Primary Outcome Measures

Change in Reactive oxygen species production [On blood and saliva: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
Reactive oxygen species production (μmol min-1) (by paramagnetic resonance)
Change in Total antioxidant capacity [On blood and saliva: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
Total antioxidant capacity (by paramagnetic resonance) (mM)
Change in Cortisol levels [On saliva: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
Cortisol (by competitive immunoassay) (ng/ml)
Change in nitrite and nitrate (NO2/NO3) concentration [On urine: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
nitrite and nitrate (NO2/NO3) concentration (by colorimetry based on the Griess reaction) (μM)
Change in inducible Nitric Oxide Synthase (iNOS) [On urine: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
inducible Nitric Oxide Synthase (by ELISA commercially available kit) (IU mL-1)
Change in aminothiols levels [On blood: Change from Baseline (T0) aminothiols concentration after the exercise test (Time 1: the day after baseline measurements), and at the completion of treatments after a second exercise test (Time 3: 5 weeks after the baseline)]
total (tot) and reduced (red) aminothiols (by fluorescence spectroscopy) (μmol L-1)
Change in Cytokines levels [On blood: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
IL-1 beta, IL-6, TNF-alfa (pg ml-1)
Change in lipid peroxidation markers [On urine: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
On urine samples, we will assess lipid peroxidation by measuring 8-isoprostane and 8-OH-deoxyguanosine concentration (by competitive immunoassay) - (pg mg-1 creatinine)
Change in Renal damage markers [On urine: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
On urine samples, we will assess renal damage by measuring creatinine (g-L-1), neopterin (μmol·mol-1 creatinine), and uric acid levels (mg/dl).
Change in 3-nitrotyrosine levels [On urine: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
3-nitrotyrosine (3-NT) (by competitive immunoassay)( nM·L-1)
Change in Stem cells mobilization [On blood: at baseline (T0), at the completion of treatments (Time 1: 5 weeks after the baseline) and 2 months after the end of treatments (Time 2)]
Stem cells (by flow cytometry) (%)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

professional athletes
performing at least 3 training sessions/week

Exclusion Criteria:

previous pneumothorax
problems with compensation maneuvers
known epilepsy
active smoker

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Human Physiology Institute, Department of Biomedical Sciences, University of Padova	Padova	Veneto	Italy	35135

Sponsors and Collaborators

University of Padova
Performa di Crocicchia Srl

Investigators

Principal Investigator: Gerardo Bosco, MD, PhD, University of Padova
Study Director: Matteo Paganini, MD, University of Padova

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Gerardo Bosco, Associate Professor, University of Padova

ClinicalTrials.gov Identifier:

NCT04366427

Other Study ID Numbers:

HEC-DSB/04-19

First Posted:

Apr 28, 2020

Last Update Posted:

Apr 30, 2021

Last Verified:

Apr 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Gerardo Bosco, Associate Professor, University of Padova

Hyperbaric Oxigenation

Study Results

No Results Posted as of Apr 30, 2021