Clinical trial NCT06946004: Normobaric Oxygen Therapy in Colorectal Cancer Patients
Official 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Colorectal Cancer (CRC)
Keywords: colorectal cancer
normobaric oxygen therapy
chemotherapy-induced anemia
oxidative stress
immune modulation
erythropoiesis
supportive cancer care
adverse effects
stress
anxiety
depression
psychological well-being
quality of life
Lead sponsor: 4th Military Clinical Hospital with Polyclinic, Poland
Sponsor class: OTHER
Collaborators: name: Wroclaw Medical University (Poland)
name: Wroclaw University of Science and Technology (Poland)
name: Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (Poland)
name: WSB Merito University in Opole (Poland)
name: Academy of Applied Sciences in Nowy Sacz (Poland)
First posted: 2025-04-27
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, double-blind, placebo-controlled clinical trial
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed description: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Erythropoietin (EPO) concentration
timeFrame: From enrollment to the end of 6th month follow-up
measure: Hypoxia-inducible factor-1α (HIF-1α)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Reticulocyte count
timeFrame: From enrollment to the end of 6th month follow-up
measure: Red blood cell (RBC)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Hemoglobin concentration (HGB)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Hematocrit
timeFrame: From enrollment to the end of 6th month follow-up
measure: Serum creatinine
timeFrame: From enrollment to the end of 6th month follow-up
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Alanine aminotransferase (ALT)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Aspartate aminotransferase (AST)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Fasting glucose
timeFrame: From enrollment to the end of 6th month follow-up
measure: Fasting insulin
timeFrame: From enrollment to the end of 6th month follow-up
measure: Lipid profile
timeFrame: From enrollment to the end of 6th month follow-up
measure: Iron metabolism (serum iron, total iron-binding capacity [TIBC]
timeFrame: From enrollment to the end of 6th month follow-up
measure: Serum albumin
timeFrame: From enrollment to the end of 6th month follow-up
measure: C-reactive protein (CRP)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Reactive oxygen species (ROS) level
timeFrame: From enrollment to the end of 6th month follow-up]
measure: Serum cortisol
timeFrame: From enrollment to the end of 6th month follow-up
measure: Gamma-aminobutyric acid (GABA)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Dopamine
timeFrame: From enrollment to the end of 6th month follow-up
measure: Serotonin
timeFrame: From enrollment to the end of 6th month follow-up
measure: Fibrinogen
timeFrame: From enrollment to the end of 6th month follow-up
measure: Glycated hemoglobin (HbA₁c)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Dehydroepiandrosterone-sulfate (DHEA-S)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Systolic blood pressure (SBP)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Diastolic blood pressure (DBP)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Heart rate (HR)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Body mass index (BMI)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Body surface area (BSA)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Waist-to-hip ratio (WHR)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Tumor necrosis factor-α (TNF-α)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Interleukin-1β (IL-1β)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Interleukin-6 (IL-6)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Interleukin-10 (IL-10)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Monocyte chemoattractant protein-1 (MCP-1/CCL2)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Macrophage inflammatory protein-1α (MIP-1α/CCL3)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Macrophage inflammatory protein-1β (MIP-1β/CCL4)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Vascular endothelial growth factor A (VEGF-A)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Platelet-derived growth factor-BB (PDGF-BB)
timeFrame: From enrollment to the end of 6th month follow-up
Secondary outcomes:
measure: Stress level (self-assessment)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Anxiety and depression levels (self-assessment)
timeFrame: From enrollment to the end of 6th month follow-up
measure: Quality of live level (self-assessment)
timeFrame: From enrollment to the end of 6th month follow-up
Other outcomes:
Locations:
city: Wroclaw
country: Poland
facility: 4th Military Clinical Hospital
Study officials:
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