Normobaric Oxygen Therapy in Colorectal Cancer Patients

Condition(s) studied

Investigational drug(s) / intervention(s)

Normobaric oxygen therapy: Patient's exposure to NBO conditions in group 1 (aNBO) including: oxygen levels of 32-40% (compared to about 21% in the atmosphere), pressure maintained at 1,500 hPa (about 1,000 hPa outside), carbon dioxide levels between 0.7-1.9% (compared to 0.03% in the atmosphere, and hydrogen levels between 0.5-1% (which is 10 to 20 thousand times higher than in the atmosphere). Exposure time in the NBO chamber will be the standard 2 hours with an additional 20 minutes for preparation and adaptation and 10 minutes for finalization and the decompression period.

Normobaric oxygen therapy: Patients' exposure to atmospheric conditions in the same NBO chamber (without normobaric conditions to provide placebo intervention as the study comparator) in group 2 (pNBO): oxygen levels about 21%, pressure maintained at about 1,000 hPa, carbon dioxide levels about o 0.03%, and hydrogen levels about 0.00005% (0.5 parts per million, like in the atmos-phere).

Study summary

Colorectal cancer (CRC) patients undergoing chemotherapy often experience anemia, oxidative stress, and immune suppression, significantly impacting their quality of life and treatment outcomes. Normobaric oxygen (NBO) therapy, which delivers oxygen at atmospheric pressure with elevated oxygen concentration, has shown a potential to enhance erythropoiesis, reduce oxidative stress, and modulate immune function. However, its efficacy in CRC patients remains underexplored. This study aims to evaluate the effects of NBO exposures on (1) supporting erythropoiesis by measuring erythropoietin (EPO) levels and hypoxia-inducible factors (HIF-1α), (2) reducing oxidative stress and improving stress and emotional well-being, and (3) modulating immune function by assessing cytokine profiles. Secondary objectives include assessing the impact of NBO on patient-reported outcome measures (PROMs) such as stress, anxiety, depression, and quality of life. This is a prospective, randomized, double-blind, placebo-controlled clinical trial. A total of 254 CRC patients undergoing chemotherapy will be randomized 1:1 to receive either active NBO therapy (n=127) or placebo NBO therapy (n=127). The intervention consists of 10 NBO sessions over five weeks. Primary outcomes include biomarkers of erythropoiesis, oxidative stress, and immune response. Secondary outcomes assess quality of life and psychological well-being. Data will be collected at baseline, mid-intervention, post-intervention, and during two follow-up visits (3- and 6-months post-intervention). The study hypothesizes that NBO therapy will improve erythropoiesis, reduce oxidative stress, and enhance immune function in CRC patients, leading to improved quality of life and clinical outcomes. Findings from this trial may establish NBO as a novel supportive therapy for CRC patients undergoing chemotherapy.

Eligibility

Primary outcome measure(s)

• Erythropoietin (EPO) concentration — From enrollment to the end of 6th month follow-up
  Erythropoietin (EPO) concentration \[mU/mL\] will be measured using a quantitative immunoassay (ELISA) at V1, V2, V3, V4, and V5.
• Hypoxia-inducible factor-1α (HIF-1α) — From enrollment to the end of 6th month follow-up
  Hypoxia-inducible factor-1α (HIF-1α) \[ng/mL\] will be measured using a quantitative immunoassay at V1, V2, V3, V4, and V5.
• Reticulocyte count — From enrollment to the end of 6th month follow-up
  Reticulocyte count \[% of total red blood cells\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.
• Red blood cell (RBC) — From enrollment to the end of 6th month follow-up
  Red blood cell (RBC) count \[10¹² cells/L\] will be measured using 5-part differential blood morphology on an automated hematology analyzer at V1, V2, V3, V4, and V5.
• Hemoglobin concentration (HGB) — From enrollment to the end of 6th month follow-up
  Hemoglobin concentration (HGB) \[g/dL\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.
• Hematocrit — From enrollment to the end of 6th month follow-up
  Hematocrit \[%\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.
• Serum creatinine — From enrollment to the end of 6th month follow-up
  Serum creatinine \[µmol/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.
• Estimated glomerular filtration rate (eGFR) — From enrollment to the end of 6th month follow-up
  Estimated glomerular filtration rate (eGFR) \[mL/min/1.73 m²\] will be calculated using the CKD-EPI equation at V1, V2, V3, V4, and V5.
• Alanine aminotransferase (ALT) — From enrollment to the end of 6th month follow-up
  Alanine aminotransferase (ALT) \[IU/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.
• Aspartate aminotransferase (AST) — From enrollment to the end of 6th month follow-up
  Aspartate aminotransferase (AST) \[IU/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.
• Fasting glucose — From enrollment to the end of 6th month follow-up
  Fasting glucose \[mmol/L\] will be measured using a hexokinase assay at V1, V2, V3, V4, and V5.
• Fasting insulin — From enrollment to the end of 6th month follow-up
  Fasting insulin \[µU/mL\] will be measured using an immunoassay at V1, V2, V3, V4, and V5.
• Lipid profile — From enrollment to the end of 6th month follow-up
  Lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides) \[mmol/L\] will be measured using enzymatic/colorimetric assays at V1, V2, V3, V4, and V5.
• Iron metabolism (serum iron, total iron-binding capacity [TIBC] — From enrollment to the end of 6th month follow-up
  Iron metabolism (serum iron, total iron-binding capacity \[TIBC\] \[µmol/L\], ferritin \[ng/mL\], vitamin B₁₂ \[pg/mL\]) will be measured using immunoassays at V1, V2, V3, V4, and V5.
• Serum albumin — From enrollment to the end of 6th month follow-up
  Serum albumin \[g/L\] will be measured using a bromcresol green assay at V1, V2, V3, V4, and V5.
• C-reactive protein (CRP) — From enrollment to the end of 6th month follow-up
  C-reactive protein (CRP) \[mg/L\] will be measured using a high-sensitivity immunoturbidimetric assay at V1, V2, V3, V4, and V5.
• Reactive oxygen species (ROS) level — From enrollment to the end of 6th month follow-up]
  Reactive oxygen species (ROS) level \[relative fluorescence units\] will be measured using a chemiluminescence assay at V1, V2, V3, V4, and V5.
• Serum cortisol — From enrollment to the end of 6th month follow-up
  Serum cortisol \[µg/dL\] will be measured using a high-sensitivity immunoassay at V1, V2, V3, V4, and V5.
• Gamma-aminobutyric acid (GABA) — From enrollment to the end of 6th month follow-up
  Gamma-aminobutyric acid (GABA) \[µmol/L\] will be measured using an enzyme-linked immunosorbent assay at V1, V2, V3, V4, and V5.
• Dopamine — From enrollment to the end of 6th month follow-up
  Dopamine \[ng/mL\] will be measured using a competitive immunoassay at V1, V2, V3, V4, and V5.
• Serotonin — From enrollment to the end of 6th month follow-up
  Serotonin \[ng/mL\] will be measured using a competitive immunoassay at V1, V2, V3, V4, and V5.
• Fibrinogen — From enrollment to the end of 6th month follow-up
  Fibrinogen \[g/L\] will be measured using the Clauss clotting assay at V1, V2, V3, V4, and V5.
• Glycated hemoglobin (HbA₁c) — From enrollment to the end of 6th month follow-up
  Glycated hemoglobin (HbA₁c) \[%\] will be measured using high-performance liquid chromatography at V1, V2, V3, V4, and V5.
• Dehydroepiandrosterone-sulfate (DHEA-S) — From enrollment to the end of 6th month follow-up
  Dehydroepiandrosterone-sulfate (DHEA-S) \[µg/dL\] will be measured using an immunoassay at V1, V2, V3, V4, and V5.
• Systolic blood pressure (SBP) — From enrollment to the end of 6th month follow-up
  Systolic blood pressure (SBP) \[mmHg\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.
• Diastolic blood pressure (DBP) — From enrollment to the end of 6th month follow-up
  Diastolic blood pressure (DBP) \[mmHg\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.
• Heart rate (HR) — From enrollment to the end of 6th month follow-up
  Heart rate (HR) \[beats per minute\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.
• Body mass index (BMI) — From enrollment to the end of 6th month follow-up
  Body mass index (BMI) \[kg/m²\] will be calculated from measured weight and height at V1, V2, V3, V4, and V5.
• Body surface area (BSA) — From enrollment to the end of 6th month follow-up
  Body surface area (BSA) \[m²\] will be calculated using the Mosteller formula from measured weight and height at V1, V2, V3, V4, and V5.
• Waist-to-hip ratio (WHR) — From enrollment to the end of 6th month follow-up
  Waist-to-hip ratio (WHR) \[ratio\] will be calculated from measured waist and hip circumferences at V1, V2, V3, V4, and V5.
• Tumor necrosis factor-α (TNF-α) — From enrollment to the end of 6th month follow-up
  Tumor necrosis factor-α (TNF-α) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Interleukin-1β (IL-1β) — From enrollment to the end of 6th month follow-up
  Interleukin-1β (IL-1β) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Interleukin-6 (IL-6) — From enrollment to the end of 6th month follow-up
  Interleukin-6 (IL-6) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Interleukin-10 (IL-10) — From enrollment to the end of 6th month follow-up
  Interleukin-10 (IL-10) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Monocyte chemoattractant protein-1 (MCP-1/CCL2) — From enrollment to the end of 6th month follow-up
  Monocyte chemoattractant protein-1 (MCP-1/CCL2) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Macrophage inflammatory protein-1α (MIP-1α/CCL3) — From enrollment to the end of 6th month follow-up
  Macrophage inflammatory protein-1α (MIP-1α/CCL3) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Macrophage inflammatory protein-1β (MIP-1β/CCL4) — From enrollment to the end of 6th month follow-up
  Macrophage inflammatory protein-1β (MIP-1β/CCL4) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Vascular endothelial growth factor A (VEGF-A) — From enrollment to the end of 6th month follow-up
  Vascular endothelial growth factor A (VEGF-A) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.
• Platelet-derived growth factor-BB (PDGF-BB) — From enrollment to the end of 6th month follow-up
  Platelet-derived growth factor-BB (PDGF-BB) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

Trial sites (1)

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