Placebo Controlled Study for Characterisation of Immunological Effects and Safety of Active O2
Condition: Healthy
Study type: Interventional

Summary: 
      The aims of this study are:

        -  Characterisation of immunological effects of Active O2 vs. placebo after ingestion
           during and post standardised strenuous exercise

        -  Characterisation of safety and tolerability of Active O2 in comparison with placebo
           after ingestion during and post standardised strenuous exercise considering Adverse
           Events observed in the study

      Moreover, the suitability of the study design shall be investigated by means of the internal
      pilot part, i.e. concerning applied procedures, selected pharmacodynamic parameters and blood
      sampling scheme.
    

Detailed description: 
      The nutritional product Active O2 (Adelholzener Alpenquellen GmbH) is a table water which
      contains an oxygen amount of 40 mg/l, a 15-fold higher amount compared to non-oxygenised
      products.

      In this study the evaluation of immunological parameters which characterise the function of
      the immune system is planned in subjects ingesting the test product Active O2 in comparison
      with a placebo group. The study rationale refers to an established mechanistic hypothesis,
      which links gastro-intestinal hypoxia during and after strenuous exercise with an impairment
      of the immune system function.

      During periods of exercise and physiological stress situations, the body primarily focuses on
      blood supply of the cardiovascular system, skeletal muscles and skin. Therefore, it is
      assumed that immunological effects during and after strenuous exercise are related - at least
      in part - to reduced blood flow in splanchnic organs which in turn leads to hypoxia induced
      damage of intestinal tissue, particularly the mucosal tissue, and to enhanced permeability
      for pathogens [1-6].

      A phenomenon well described in scientific literature is related to athletes suffering from
      infections, particularly in the upper respiratory tract, after strenuous exercise.
      Significantly higher endotoxin concentrations (lipopolysaccharides) could be detected in the
      blood of athletes after strenuous competitions when compared to control groups [7].

      In scientific studies, a decrease in the number of circulating immune cells as well as a
      reduced host defence function after strenuous and sustained exercise has been demonstrated
      in-vivo and by application of immunological in-vitro methods. Significant decreases in
      T-lymphocytes, T-helper cells type 1 as well as in Natural Killer cells (NK) could be shown.
      However, B-cells and T-helper cells type 2 are not affected in a comparable magnitude [8-10].

      In one study a significant increase in regulatory T-cells (Treg) has been assessed after 45
      min of swim exercise in adolescents [11]. These cells play a major role in the inhibition of
      effector T cell function and thus have a pronounced immunosuppressive effect. Furthermore, it
      has been shown that Treg-cell activity is directly linked to the occurrence of hypoxia in
      damaged tissues [12].

      Immune responses due to exercise are complex and depend on numerous additional factors (e.g.
      stress hormones, reactive oxygen species) as well as on the intensity of exercise level
      [13-15].

      Nonetheless, oxygen susceptibility of regulatory immunocompetent cells as well as integrity
      of the mucosal barrier function may play an important role in protection and/or modification
      of the immune response including the integrity of epithelial tight junctions and M-cell
      related transcytosis of pathogens to highly organised lymphoid structures for effective
      immune responses [4; 12; 16]. A strong correlation between intestinal hypoxia during
      strenuous exercise and the magnitude of intestinal mucosa damage has been demonstrated by
      plasma levels of the surrogate parameter intestinal fatty acid binding protein (I-FABP), a
      specific biomarker for mucosal damage in the small intestine [4; 17].

      The hypothesis to be investigated in this study is that the oxygen content of Active O2 may -
      at least in part - compensate the hypoxic situation in the surface of the gut wall, when
      ingested during and after exercise. Luminal supply of oxygenated water potentially might
      protect mucosal tissue from ischemia related damage and could modulate immune responses. As a
      consequence, the overall situation of the immune system might improve. Such an effect should
      be reflected in the pharmacodynamic parameters determined in this study.

      A first interim analysis of the previous pilot part of this study, including the results of
      12 healthy subjects, revealed statistically significant differences between both treatments
      for leukocytes, CD8+-lymphocytes and NK cells. Significant differences in cytokine production
      and additional immunological parameters were not detectable in comparison of both treatments
      and no trends were observed which might indicate any treatment effect. Therefore, the second
      part of this clinical trial will be performed with a focus on the pharmacodynamic parameters
      from the pilot part for which statistically significant differences between treatments have
      been observed. However, additional inclusion of I FABP analysis is considered reasonable as
      this surrogate parameter specifically reflects quantifiable impairment and potential local
      oxygen effects on intestinal mucosa barrier function.

      According to EU regulation No 1924/2006 on nutrition and health claims made on foods,
      nutrition producing companies must show scientific data with substantiation as a prerequisite
      for advertisement dealing with health related claims [17]. Thus, the clinical trial is
      planned to further investigate a potentially beneficial effect of Active O2 when ingested
      during and after exercise.
    

Intervention name(s): Active O2; Adelholzener Mineralwasser
Intervention type(s): Other; Other
Intervention description(s): oxygenised table water containing at least 20 mg O2 per 500 ml (15-fold higher content in comparison to placebo), further excipients: natural mineral water: carbonic acid, oxygen, sodium, potassium, magnesium, calcium, fluoride, chloride, nitrate, sulfate, hydrocarbonate (according to the summary of analysis); natural mineral water containing the following ingredients: carbonic acid, sodium, potassium, magnesium, calcium, fluoride, chloride, nitrate, sulphate, hydrocarbonate (according to the summary of analysis)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: immunological effects; Active O2; strenuous exercise; procedures; pharmacodynamic parameters; blood sampling scheme