Normobaric Oxygen Therapy in Colorectal Cancer Patients

NCT06946004 | Not Yet Recruiting DMC

• 1 other identifier: 2024/ABM/02/00007
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (39)

• Erythropoietin (EPO) concentration

  Erythropoietin (EPO) concentration \[mU/mL\] will be measured using a quantitative immunoassay (ELISA) at V1, V2, V3, V4, and V5.

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

• Hypoxia-inducible factor-1α (HIF-1α)

  Hypoxia-inducible factor-1α (HIF-1α) \[ng/mL\] will be measured using a quantitative immunoassay at V1, V2, V3, V4, and V5.

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

• Reticulocyte count

  Reticulocyte count \[% of total red blood cells\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.

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

• Red blood cell (RBC)

  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.

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

• Hemoglobin concentration (HGB)

  Hemoglobin concentration (HGB) \[g/dL\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.

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

• Hematocrit

  Hematocrit \[%\] will be measured using an automated hematology analyzer at V1, V2, V3, V4, and V5.

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

• Serum creatinine

  Serum creatinine \[µmol/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.

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

• Estimated glomerular filtration rate (eGFR)

  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.

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

• Alanine aminotransferase (ALT)

  Alanine aminotransferase (ALT) \[IU/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.

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

• Aspartate aminotransferase (AST)

  Aspartate aminotransferase (AST) \[IU/L\] will be measured using an enzymatic assay at V1, V2, V3, V4, and V5.

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

• Fasting glucose

  Fasting glucose \[mmol/L\] will be measured using a hexokinase assay at V1, V2, V3, V4, and V5.

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

• Fasting insulin

  Fasting insulin \[µU/mL\] will be measured using an immunoassay at V1, V2, V3, V4, and V5.

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

• Lipid profile

  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.

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

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

  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.

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

• Serum albumin

  Serum albumin \[g/L\] will be measured using a bromcresol green assay at V1, V2, V3, V4, and V5.

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

• C-reactive protein (CRP)

  C-reactive protein (CRP) \[mg/L\] will be measured using a high-sensitivity immunoturbidimetric assay at V1, V2, V3, V4, and V5.

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

• Reactive oxygen species (ROS) level

  Reactive oxygen species (ROS) level \[relative fluorescence units\] will be measured using a chemiluminescence assay at V1, V2, V3, V4, and V5.

  From enrollment to the end of 6th month follow-up]

• Serum cortisol

  Serum cortisol \[µg/dL\] will be measured using a high-sensitivity immunoassay at V1, V2, V3, V4, and V5.

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

• Gamma-aminobutyric acid (GABA)

  Gamma-aminobutyric acid (GABA) \[µmol/L\] will be measured using an enzyme-linked immunosorbent assay at V1, V2, V3, V4, and V5.

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

• Dopamine

  Dopamine \[ng/mL\] will be measured using a competitive immunoassay at V1, V2, V3, V4, and V5.

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

• Serotonin

  Serotonin \[ng/mL\] will be measured using a competitive immunoassay at V1, V2, V3, V4, and V5.

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

• Fibrinogen

  Fibrinogen \[g/L\] will be measured using the Clauss clotting assay at V1, V2, V3, V4, and V5.

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

• Glycated hemoglobin (HbA₁c)

  Glycated hemoglobin (HbA₁c) \[%\] will be measured using high-performance liquid chromatography at V1, V2, V3, V4, and V5.

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

• Dehydroepiandrosterone-sulfate (DHEA-S)

  Dehydroepiandrosterone-sulfate (DHEA-S) \[µg/dL\] will be measured using an immunoassay at V1, V2, V3, V4, and V5.

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

• Systolic blood pressure (SBP)

  Systolic blood pressure (SBP) \[mmHg\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.

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

• Diastolic blood pressure (DBP)

  Diastolic blood pressure (DBP) \[mmHg\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.

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

• Heart rate (HR)

  Heart rate (HR) \[beats per minute\] will be measured using an automated sphygmomanometer at V1, V2, V3, V4, and V5.

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

• Body mass index (BMI)

  Body mass index (BMI) \[kg/m²\] will be calculated from measured weight and height at V1, V2, V3, V4, and V5.

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

• Body surface area (BSA)

  Body surface area (BSA) \[m²\] will be calculated using the Mosteller formula from measured weight and height at V1, V2, V3, V4, and V5.

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

• Waist-to-hip ratio (WHR)

  Waist-to-hip ratio (WHR) \[ratio\] will be calculated from measured waist and hip circumferences at V1, V2, V3, V4, and V5.

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

• Tumor necrosis factor-α (TNF-α)

  Tumor necrosis factor-α (TNF-α) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Interleukin-1β (IL-1β)

  Interleukin-1β (IL-1β) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Interleukin-6 (IL-6)

  Interleukin-6 (IL-6) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Interleukin-10 (IL-10)

  Interleukin-10 (IL-10) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Monocyte chemoattractant protein-1 (MCP-1/CCL2)

  Monocyte chemoattractant protein-1 (MCP-1/CCL2) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Macrophage inflammatory protein-1α (MIP-1α/CCL3)

  Macrophage inflammatory protein-1α (MIP-1α/CCL3) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Macrophage inflammatory protein-1β (MIP-1β/CCL4)

  Macrophage inflammatory protein-1β (MIP-1β/CCL4) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Vascular endothelial growth factor A (VEGF-A)

  Vascular endothelial growth factor A (VEGF-A) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

• Platelet-derived growth factor-BB (PDGF-BB)

  Platelet-derived growth factor-BB (PDGF-BB) \[pg/mL\] will be measured using a multiplex immunoassay (Luminex) at V1, V2, V3, V4, and V5.

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

Secondary Outcomes (3)

• Stress level (self-assessment)

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

• Anxiety and depression levels (self-assessment)

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

• Quality of live level (self-assessment)

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

Study Arms (2)

active NBO therapy (n=127)

EXPERIMENTAL

Patient's exposure to NBO conditions in group 1 (aNBO)

Device: Normobaric oxygen therapy

placebo NBO therapy (n=127)

PLACEBO COMPARATOR

Patients' exposure to atmospheric conditions in the same NBO chamber without normobaric conditions in group 2 (pNBO)

Device: Normobaric oxygen therapy

Interventions

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.

active NBO therapy (n=127)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• 4th Military Clinical Hospital with Polyclinic, Poland: lead
• Wroclaw Medical University (Poland): collaborator
• Wroclaw University of Science and Technology (Poland): collaborator
• Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences (Poland): collaborator
• WSB Merito University in Opole (Poland): collaborator
• Academy of Applied Sciences in Nowy Sacz (Poland): collaborator

Study Sites (1)

4th Military Clinical Hospital

Wroclaw, 50-981, Poland

Location

Related Publications (9)

• Lin CH, Su WH, Chen YC, Feng PH, Shen WC, Ong JR, Wu MY, Wong CS. Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018 Sep;97(39):e12456. doi: 10.1097/MD.0000000000012456.

  PMID: 30278526 BACKGROUND

• Bloch Y, Belmaker RH, Shvartzman P, Romem P, Bolotin A, Bersudsky Y, Azab AN. Normobaric oxygen treatment for mild-to-moderate depression: a randomized, double-blind, proof-of-concept trial. Sci Rep. 2021 Sep 23;11(1):18911. doi: 10.1038/s41598-021-98245-9.

  PMID: 34556722 BACKGROUND

• Kujawski S, Slomko J, Morten KJ, Murovska M, Buszko K, Newton JL, Zalewski P. Autonomic and Cognitive Function Response to Normobaric Hyperoxia Exposure in Healthy Subjects. Preliminary Study. Medicina (Kaunas). 2020 Apr 10;56(4):172. doi: 10.3390/medicina56040172.

  PMID: 32290164 BACKGROUND

• De Bels D, Theunissen S, Devriendt J, Germonpre P, Lafere P, Valsamis J, Snoeck T, Meeus P, Balestra C. The 'normobaric oxygen paradox': does it increase haemoglobin? Diving Hyperb Med. 2012 Jun;42(2):67-71.

  PMID: 22828812 BACKGROUND

• Saleh EAM, Al-Dolaimy F, Qasim Almajidi Y, Baymakov S, Kader M MA, Ullah MI, Abbas AHR, Khlewee IH, Bisht YS, Alsaalamy AH. Oxidative stress affects the beginning of the growth of cancer cells through a variety of routes. Pathol Res Pract. 2023 Sep;249:154664. doi: 10.1016/j.prp.2023.154664. Epub 2023 Jul 1.

  PMID: 37573621 BACKGROUND

• Noman MZ, Hasmim M, Lequeux A, Xiao M, Duhem C, Chouaib S, Berchem G, Janji B. Improving Cancer Immunotherapy by Targeting the Hypoxic Tumor Microenvironment: New Opportunities and Challenges. Cells. 2019 Sep 14;8(9):1083. doi: 10.3390/cells8091083.

  PMID: 31540045 BACKGROUND

• Bozzini C, Busti F, Marchi G, Vianello A, Cerchione C, Martinelli G, Girelli D. Anemia in patients receiving anticancer treatments: focus on novel therapeutic approaches. Front Oncol. 2024 Apr 2;14:1380358. doi: 10.3389/fonc.2024.1380358. eCollection 2024.

  PMID: 38628673 BACKGROUND

• Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012 Aug;13(8):790-801. doi: 10.1016/S1470-2045(12)70211-5. Epub 2012 Jun 1.

  PMID: 22658655 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Anxiety Disorders; Depression; Psychological Well-Being

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Mental Disorders; Behavioral Symptoms; Behavior; Personal Satisfaction

Central Study Contacts

Beata Jankowska-Polańska Prof., PhD

CONTACT

+48 71 727 41 52; dyrektor@cwbk.4wsk.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be double-blinded, ensuring that neither patients nor the research team involved in data analysis know the allocation to active or placebo NBO, preserving objectivity in outcome assessment. Patients and clinical staff (excluding NBO operators who administer the therapy) are blinded to treatment allocation.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective, randomized, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 27, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

PL (1)