# The Potential of Normobaric Oxygen Therapy to Enhance Erythropoiesis, Reduce Oxidative Stress, and Modulate Immune Function in Colorectal Cancer Patients Undergoing Chemotherapy: Study Protocol for a Prospective, Randomized, Double-Blind, Placebo-Controlled Trial (NBO-ONCO)

## TL;DR

This study explores whether breathing higher oxygen levels can help colorectal cancer patients during chemotherapy by improving blood cell production, reducing stress, and boosting immunity.

## Contribution

The study introduces a novel clinical trial protocol to evaluate normobaric oxygen therapy's effects on erythropoiesis, oxidative stress, and immune function in colorectal cancer patients.

## Key findings

- Normobaric oxygen therapy may enhance erythropoiesis through increased EPO and HIF-1α levels.
- NBO could reduce oxidative stress and improve psychological well-being in CRC patients.
- The therapy may modulate immune function by altering cytokine profiles.

## Abstract

Colorectal cancer is a major global health challenge, and patients undergoing chemotherapy often experience anemia, immune dysfunction, and oxidative stress, which can negatively affect treatment outcomes and quality of life. A simple and non-invasive approach like normobaric oxygen therapy may help by boosting red blood cell production, reducing inflammation, and strengthening the immune system. This study aims to evaluate its effectiveness in patients with colorectal cancer receiving chemotherapy, assessing its impact on erythropoiesis, immune function, oxidative stress, and psychological well-being. By exploring this potential therapy, we hope to uncover a safer and more accessible way to support cancer patients during treatment with chemotherapy. If proven beneficial, normobaric oxygen therapy could be integrated into oncology treatment protocols, enhancing patient outcomes and supporting overall quality of life.

Background/Objectives: 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 an elevated oxygen concentration, has shown the 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 factor 1-alpha (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. Methods: 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, study group) or placebo NBO therapy (n = 127, control group). The intervention will consist 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). Results: 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. Conclusions: Findings from this trial may establish NBO as a novel supportive therapy for CRC patients undergoing chemotherapy.