Enriched Oxygen Mixtures in Athletes

NCT04366427 | Completed Phase 2

• 1 other identifier: HEC-DSB/04-19
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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:

1. 1.HBO can reduce oxidative stress and induce stem cell mobilization in healthy professional athletes;
2. 2.hyperoxic mixtures can reduce oxidative stress and induce stem cells mobilization in healthy professional athletes;
3. 3.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.

Conditions

Oxidative Stress; Stem Cell Research

Keywords

Hyperbaric Oxigenation; Sport Medicine; Training; Recovery; Oxidative Stress; Stem Cell Research

Outcome Measures

Primary Outcomes (11)

• Change in Reactive oxygen species production

  Reactive oxygen species production (μmol min-1) (by paramagnetic resonance)

  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)

• Change in Total antioxidant capacity

  Total antioxidant capacity (by paramagnetic resonance) (mM)

  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)

• Change in Cortisol levels

  Cortisol (by competitive immunoassay) (ng/ml)

  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)

• Change in nitrite and nitrate (NO2/NO3) concentration

  nitrite and nitrate (NO2/NO3) concentration (by colorimetry based on the Griess reaction) (μM)

  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)

• Change in inducible Nitric Oxide Synthase (iNOS)

  inducible Nitric Oxide Synthase (by ELISA commercially available kit) (IU mL-1)

  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)

• Change in aminothiols levels

  total (tot) and reduced (red) aminothiols (by fluorescence spectroscopy) (μmol L-1)

  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)

• Change in Cytokines levels

  IL-1 beta, IL-6, TNF-alfa (pg ml-1)

  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)

• Change in lipid peroxidation markers

  On urine samples, we will assess lipid peroxidation by measuring 8-isoprostane and 8-OH-deoxyguanosine concentration (by competitive immunoassay) - (pg mg-1 creatinine)

  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)

• Change in Renal damage markers

  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).

  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)

• Change in 3-nitrotyrosine levels

  3-nitrotyrosine (3-NT) (by competitive immunoassay)( nM·L-1)

  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)

• Change in Stem cells mobilization

  Stem cells (by flow cytometry) (%)

  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)

Study Arms (5)

Low-pressure hyperbaric oxygenation (L-HBO)

EXPERIMENTAL

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

Standard-pressure hyperbaric oxygenation (HBO)

EXPERIMENTAL

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

Control

NO INTERVENTION

Control group of athletes, no intervention.

30% O2

EXPERIMENTAL

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

50% O2

EXPERIMENTAL

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

Interventions

L-HBO COMBINATION_PRODUCT

as previously described.

Also known as: Low Pressure Oxygenation

Low-pressure hyperbaric oxygenation (L-HBO)

HBO COMBINATION_PRODUCT

as previously described.

Also known as: Standard Pressure Oxygenation

Standard-pressure hyperbaric oxygenation (HBO)

30% O2 COMBINATION_PRODUCT

as previously described

Also known as: 30% O2 mixture

30% O2

50% O2 COMBINATION_PRODUCT

as previously described

Also known as: 50% O2 mixture

50% O2

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• professional athletes
• performing at least 3 training sessions/week

You may not qualify if:

• previous pneumothorax
• problems with compensation maneuvers
• known epilepsy
• active smoker

Sponsors & Collaborators

• University of Padova: lead
• Performa di Crocicchia Srl: collaborator

Study Sites (1)

Human Physiology Institute, Department of Biomedical Sciences, University of Padova

Padua, Veneto, 35135, Italy

Location

Related Publications (12)

• Pedoto A, Nandi J, Yang ZJ, Wang J, Bosco G, Oler A, Hakim TS, Camporesi EM. Beneficial effect of hyperbaric oxygen pretreatment on lipopolysaccharide-induced shock in rats. Clin Exp Pharmacol Physiol. 2003 Jul;30(7):482-8. doi: 10.1046/j.1440-1681.2003.03865.x.

  PMID: 12823263 BACKGROUND

• Bosco G, Yang ZJ, Nandi J, Wang J, Chen C, Camporesi EM. Effects of hyperbaric oxygen on glucose, lactate, glycerol and anti-oxidant enzymes in the skeletal muscle of rats during ischaemia and reperfusion. Clin Exp Pharmacol Physiol. 2007 Jan-Feb;34(1-2):70-6. doi: 10.1111/j.1440-1681.2007.04548.x.

  PMID: 17201738 BACKGROUND

• Yang ZJ, Xie Y, Bosco GM, Chen C, Camporesi EM. Hyperbaric oxygenation alleviates MCAO-induced brain injury and reduces hydroxyl radical formation and glutamate release. Eur J Appl Physiol. 2010 Feb;108(3):513-22. doi: 10.1007/s00421-009-1229-9. Epub 2009 Oct 23.

  PMID: 19851780 BACKGROUND

• Bosco G, Yang ZJ, Di Tano G, Camporesi EM, Faralli F, Savini F, Landolfi A, Doria C, Fano G. Effect of in-water oxygen prebreathing at different depths on decompression-induced bubble formation and platelet activation. J Appl Physiol (1985). 2010 May;108(5):1077-83. doi: 10.1152/japplphysiol.01058.2009. Epub 2010 Feb 25.

  PMID: 20185629 BACKGROUND

• Morabito C, Bosco G, Pilla R, Corona C, Mancinelli R, Yang Z, Camporesi EM, Fano G, Mariggio MA. Effect of pre-breathing oxygen at different depth on oxidative status and calcium concentration in lymphocytes of scuba divers. Acta Physiol (Oxf). 2011 May;202(1):69-78. doi: 10.1111/j.1748-1716.2010.02247.x. Epub 2011 Mar 1.

  PMID: 21199400 BACKGROUND

• Nasole E, Nicoletti C, Yang ZJ, Girelli A, Rubini A, Giuffreda F, Di Tano A, Camporesi E, Bosco G. Effects of alpha lipoic acid and its R+ enantiomer supplemented to hyperbaric oxygen therapy on interleukin-6, TNF-alpha and EGF production in chronic leg wound healing. J Enzyme Inhib Med Chem. 2014 Apr;29(2):297-302. doi: 10.3109/14756366.2012.759951. Epub 2013 Jan 30.

  PMID: 23360079 BACKGROUND

• Camporesi EM, Bosco G. Mechanisms of action of hyperbaric oxygen therapy. Undersea Hyperb Med. 2014 May-Jun;41(3):247-52.

  PMID: 24984320 BACKGROUND

• Bosco G, Vezzani G, Mrakic Sposta S, Rizzato A, Enten G, Abou-Samra A, Malacrida S, Quartesan S, Vezzoli A, Camporesi E. Hyperbaric oxygen therapy ameliorates osteonecrosis in patients by modulating inflammation and oxidative stress. J Enzyme Inhib Med Chem. 2018 Dec;33(1):1501-1505. doi: 10.1080/14756366.2018.1485149.

  PMID: 30274530 BACKGROUND

• Moskowitz A, Andersen LW, Huang DT, Berg KM, Grossestreuer AV, Marik PE, Sherwin RL, Hou PC, Becker LB, Cocchi MN, Doshi P, Gong J, Sen A, Donnino MW. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit Care. 2018 Oct 29;22(1):283. doi: 10.1186/s13054-018-2217-4.

  PMID: 30373647 BACKGROUND

• Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: a 30 year history. Dyn Med. 2009 Jan 13;8:1. doi: 10.1186/1476-5918-8-1.

  PMID: 19144121 BACKGROUND

• Menzies P, Menzies C, McIntyre L, Paterson P, Wilson J, Kemi OJ. Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery. J Sports Sci. 2010 Jul;28(9):975-82. doi: 10.1080/02640414.2010.481721.

  PMID: 20544484 BACKGROUND

• Van Hooren B, Peake JM. Do We Need a Cool-Down After Exercise? A Narrative Review of the Psychophysiological Effects and the Effects on Performance, Injuries and the Long-Term Adaptive Response. Sports Med. 2018 Jul;48(7):1575-1595. doi: 10.1007/s40279-018-0916-2.

  PMID: 29663142 BACKGROUND

Study Officials

• Gerardo Bosco, MD, PhD

  University of Padova

  PRINCIPAL INVESTIGATOR

• Matteo Paganini, MD

  University of Padova

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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;

Study Record Dates

• First Submitted: March 4, 2020
• First Posted: April 28, 2020
• Study Start: September 15, 2020
• Primary Completion: November 15, 2020
• Study Completion: December 31, 2020
• Last Updated: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)