Skip to main content
OpenTrials
Not Yet Recruiting

NCT Number: NCT06946004

Normobaric Oxygen Therapy in Colorectal Cancer Patients

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.

Not Yet Recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Colorectal Cancer (CRC) Anxiety Disorders Behavior Behavioral Symptoms Colonic Diseases Colorectal Neoplasms Depression Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Mental Disorders Neoplasms Neoplasms by Site Personal Satisfaction Psychological Well-Being Rectal Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

4th Military Clinical Hospital

Wroclaw, 50-981, Poland

Location contact

Beata Freier MD, PhD

SUB_INVESTIGATOR

Beata Jankowska-Polańska Prof., PhD

CONTACT

[email protected]

+48 71 727 41

Edyta Pawlak Prof., PhD

SUB_INVESTIGATOR

Jacek Polański Dr, PhD

PRINCIPAL_INVESTIGATOR

About this study

The intervention will involve NBO as a supportive treatment for CRC patients undergoing chemotherapy. The NBO protocol consists of regular sessions in a normobaric chamber where patients are exposed to controlled oxygen levels aimed at reducing ox-idative stress, supporting erythropoiesis, and modulating immune function. Patients in the CRC group will undergo 10 NBO sessions across five weeks, with two sessions weekly.

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 the finalization and decompression period.

Patients' exposure to atmospheric conditions in the same NBO chamber (without normobaric conditions to provide sham-placebo intervention) 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). The primary comparator in this study is the placebo NBO group (CRC patients; n=127) for CRC patients, which serves to differentiate the specific effects of active NBO from the natural course of treatment without enhanced oxygen exposure.

The patient assessment scheme contains six visits from V0 to V5 with subsequent analytical packages with detailed explanation in 2.8. section. The patient assessment schedule consists of six visits, from V0 to V5, each including specific evaluations and interventions. The study begins with V0 (prequalification/screening), where patient consent is obtained, medical history is collected, and baseline data are recorded. V1 (randomization and pre-test visit) involves the initial assessments, including anemia, stress, immune, genetic markers, and patient-reported outcomes (PROMs). Following this, the first phase of the NBO intervention (sessions 1-5) takes place over five weeks. At V2 (midpoint evaluation), the same set of assessments is repeated to track progress, followed by the second phase of the NBO intervention (sessions 6-10) conducted over the next five weeks. V3 (finalization and post-test visit) marks the completion of the intervention, with a final round of primary and secondary outcome assessments. The study then proceeds with two follow-up visits: V4 (3-months post-NBO) and V5 (6-months post-NBO), where anemia, stress, immune, genetic markers, and PROMs are reassessed to evaluate the long-term effects of the intervention.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • age between 18 and 80 years (participants must be adults)
  • diagnosed with CRC (stage II-IV, scheduled for standard chemotherapy (for study and control groups)
  • baseline hemoglobin levels above 10 g/dL
  • no concurrent hematologic malignancies
  • eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (ensuring participants are ambulatory and capable of self-care)
  • life expectancy of at least 12 months (participants are expected to survive the duration of the study)
  • ability and willingness to comply with all study procedures and schedules (including NBO therapy sessions and follow-up visits)
  • adequate organ function as determined by laboratory tests (liver function tests - ALT, AST), renal function tests (serum creatinine, eGFR)
  • women of childbearing potential must have a negative pregnancy test prior to enrollment and agree to use effective contraception during the study (to ensure safety for potential pregnancies)
  • written informed consent obtained prior to any study-related procedures (participants must understand and agree to all aspects of the study).

Exclusion criteria

  • age under 18 years or over 80 years
  • severe cardiovascular or respiratory conditions (e.g., unstable angina, recent myocardial infarction, advanced COPD)
  • severe anemia (hemoglobin <10 g/dL) or any hemolytic disorder that could confound study outcomes
  • uncontrolled diabetes mellitus (e.g., HbA1c >8.0% or poor glycemic control requiring frequent hospitalizations)
  • pregnancy or breastfeeding
  • severe infection or immunocompromised status unrelated to cancer (e.g., advanced HIV infection)
  • current psychiatric or neurological disorders that could interfere with study participation
  • participation in other investigational therapies within the last 30 days; (9) lack of written informed consent for study participation
  • autoimmune or inflammatory conditions (e.g., lupus, rheumatoid arthritis on immunosuppressive therapy) that significantly alter immune responses
  • presence of any contraindication for NBO therapy (e.g., active bleeding, acute infections, inflammation of the optic nerve, epilepsy or seizures, uncontrolled diabetes as noted above, pneumothorax, emphysema, electronic implants).

Treatment and study plan

Normobaric oxygen therapy

Device

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.

Primary outcomes

  1. Erythropoietin (EPO) concentration

    Time frame: 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.

  2. Hypoxia-inducible factor-1α (HIF-1α)

    Time frame: 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.

  3. Reticulocyte count

    Time frame: 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.

  4. Red blood cell (RBC)

    Time frame: 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.

  5. Hemoglobin concentration (HGB)

    Time frame: 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.

  6. Hematocrit

    Time frame: 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.

  7. Serum creatinine

    Time frame: 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.

  8. Estimated glomerular filtration rate (eGFR)

    Time frame: 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.

  9. Alanine aminotransferase (ALT)

    Time frame: 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.

  10. Aspartate aminotransferase (AST)

    Time frame: 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.

  11. Fasting glucose

    Time frame: 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.

  12. Fasting insulin

    Time frame: 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.

  13. Lipid profile

    Time frame: 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.

  14. Iron metabolism (serum iron, total iron-binding capacity [TIBC]

    Time frame: 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.

  15. Serum albumin

    Time frame: 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.

  16. C-reactive protein (CRP)

    Time frame: 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.

  17. Reactive oxygen species (ROS) level

    Time frame: 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.

  18. Serum cortisol

    Time frame: 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.

  19. Gamma-aminobutyric acid (GABA)

    Time frame: 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.

  20. Dopamine

    Time frame: 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.

  21. Serotonin

    Time frame: 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.

  22. Fibrinogen

    Time frame: 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.

  23. Glycated hemoglobin (HbA₁c)

    Time frame: 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.

  24. Dehydroepiandrosterone-sulfate (DHEA-S)

    Time frame: 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.

  25. Systolic blood pressure (SBP)

    Time frame: 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.

  26. Diastolic blood pressure (DBP)

    Time frame: 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.

  27. Heart rate (HR)

    Time frame: 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.

  28. Body mass index (BMI)

    Time frame: 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.

  29. Body surface area (BSA)

    Time frame: 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.

  30. Waist-to-hip ratio (WHR)

    Time frame: 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.

  31. Tumor necrosis factor-α (TNF-α)

    Time frame: 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.

  32. Interleukin-1β (IL-1β)

    Time frame: 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.

  33. Interleukin-6 (IL-6)

    Time frame: 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.

  34. Interleukin-10 (IL-10)

    Time frame: 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.

  35. Monocyte chemoattractant protein-1 (MCP-1/CCL2)

    Time frame: 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.

  36. Macrophage inflammatory protein-1α (MIP-1α/CCL3)

    Time frame: 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.

  37. Macrophage inflammatory protein-1β (MIP-1β/CCL4)

    Time frame: 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.

  38. Vascular endothelial growth factor A (VEGF-A)

    Time frame: 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.

  39. Platelet-derived growth factor-BB (PDGF-BB)

    Time frame: 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.

Secondary outcomes

  1. Stress level (self-assessment)

    Time frame: From enrollment to the end of 6th month follow-up

    The Perceived Stress Questionnaire (PSQ-30) is a 30-item self-report instrument designed to assess perceived stress over the previous month. Each item is rated on a 4-point Likert scale (1 = "almost never" to 4 = "usually"), yielding a raw score that can range from 30 (minimum) to 120 (maximum). Higher raw scores indicate greater perceived stress (worse outcome). The PSQ-30 will be administered at V1, V2, V3, V4, and V5.

  2. Anxiety and depression levels (self-assessment)

    Time frame: From enrollment to the end of 6th month follow-up

    The Hospital Anxiety and Depression Scale (HADS) is a 14-item self-report questionnaire comprising two subscales: HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D). Each subscale contains 7 items scored on a 4-point Likert scale (0 = "not at all" to 3 = "very often"), yielding subscale scores from 0 (minimum) to 21 (maximum). Higher scores indicate greater symptom severity (worse outcome). The HADS total score (sum of HADS-A and HADS-D) ranges from 0 to 42. The HADS will be administered at V1, V2, V3, V4, and V5.

  3. Quality of live level (self-assessment)

    Time frame: From enrollment to the end of 6th month follow-up

    EuroQol Five-Dimension Five-Level questionnaire (EQ-5D-5L) index score [-0.59 to 1.00; higher = better health] will be derived from five domains-mobility, self-care, usual activities, pain/discomfort, and anxiety/depression-each rated on a 5-point scale (1 = no problems to 5 = extreme problems). Health states will be converted to a single index value using the Polish EQ-5D-5L value set. The EQ-5D-5L will be administered at V1, V2, V3, V4, and V5.

Study contacts

Contact information is provided by the study sponsor or research team.

Beata Jankowska-Polańska Prof., PhD

CONTACT

[email protected]

+48 71 727 41 52

Sponsors and collaborators

Lead sponsor

4th Military Clinical Hospital with Polyclinic, Poland

Other

Collaborators

  • Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (Poland)
  • University of Applied Sciences in Nowy Sacz
  • WSB Merito University in Opole (Poland)
  • Wroclaw Medical University
  • Wroclaw University of Science and Technology (Poland)

Registry information

Official study title

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)

Acronym: NBO-ONCO

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Apr 27, 2025
Registry last updated
Apr 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.