Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2026 and 2029.

Official title

Prospective and Observational Study of Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2026 and 2029. Prospective Study EPOOzo-2.

Overview

The main objective of this study is to analyze the impact on the health-related quality of life of patients with refractory symptoms who have been referred to the Dr. Negrín University Hospital Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between January 2026 and December 2029. Additionally, the study aims to evaluate several specific symptoms, hyperspectral and thermal images, non-invasive clinical parameters related to the Autonomic Nervous System (such as heart rate variability, electrochemical skin conductance, and vibration perception thresholds), oxidative stress and inflammatory parameters, and gut microbiota composition.

Detailed description

Patients are referred to the Chronic Pain Unit in the absence or failure of standard treatment, or when the standard treatment is associated with high morbidity or high risk. Frequently, these patients present alterations in self-perceived health-related quality of life (HRQoL), anxiety, depression, and other symptoms such as radiation-induced pelvic toxicity or chemotherapy-induced peripheral neuropathy (CIPN).

This prospective observational study (EPOOzo-2) aims to evaluate the effect of adjuvant symptomatic/palliative ozone therapy on HRQoL and potential changes from baseline. Specifically, it incorporates new non-invasive technologies to objectively assess microcirculation, neuropathy and autonomic regulation.

Main Objectives:

1\. Analyze the impact on HRQoL of patients with refractory symptoms treated with ozone.

Secondary Objectives: Depending on the clinical case, analyze the impact of ozone treatment on: 2. Anxiety and depression. 3. Treated symptoms (e.g., pain, paresthesia). 4. Fatigue. 5. Toxicity grade (in cancer patients). 6. Non-invasive clinical parameters related to the Autonomic Nervous System (central and peripheral) and somatosensory function. 7. Biochemical parameters and gut microbiome analysis (in patients with systemic/rectal ozone).

Methodology: Prospective and observational study of patients referred for symptomatic/palliative ozone therapy between January 2026 and December 2029.

Assessments at weeks: 0 (baseline), 16 (end of O3/O2 treatment), 28 (12 weeks after the end of ozone), and 40 (24 weeks after the end of ozone).

Interventions

• Procedure Ozone Therapy
  Systemic (rectal, autohemotherapy) and/or local ozone administration (cutaneous, intravaginal, intravesical). Dosage, frequency, and duration will depend on the symptoms treated and clinical evolution. Usually planned 40 sessions over 4 months.

Primary outcome measures

• Change from Baseline in Health-Related Quality of Life by the "EQ-5D-5L" Questionnaire (at the end of ozone therapy). [Time frame: At the end of ozone therapy (approx. week 16).]

Secondary outcome measures (12)

• Change from Baseline in Health-Related Quality of Life by the "EQ-5D-5L" Questionnaire (at 12 weeks after the end of ozone therapy). [Time frame: At 12 weeks after the end of ozone therapy (approx. week 28).]
• Change from Baseline in Health-Related Quality of Life by the "EQ-5D-5L" Questionnaire (at 24 weeks after the end of ozone therapy). [Time frame: At 24 weeks after the end of ozone therapy (approx. week 40).]
• Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at the end of ozone therapy). [Time frame: At the end of ozone therapy (approx. week 16).]
• Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at 12 weeks after the end of ozone therapy). [Time frame: At 12 week after the end of ozone therapy (approx. week 28).]
• Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at 24 weeks after the end of ozone therapy). [Time frame: At 24 week after the end of ozone therapy (approx. week 40).]
• Change from Baseline in Health-Related Quality of Life by the "QLQ-C30" Questionnaire (only in cancer patients). (At the end of ozone therapy). [Time frame: At the end of ozone therapy (approx. week 16).]
• Change from Baseline in Health-Related Quality of Life by the "QLQ-C30" Questionnaire (only in cancer patients). (At 12 weeks after the end of ozone therapy). [Time frame: At 12 weeks after the end of ozone therapy (approx. week 28).]
• Change from Baseline in Health-Related Quality of Life by the "QLQ-C30" Questionnaire (only in cancer patients). (At 24 weeks after the end of ozone therapy). [Time frame: At 24 weeks after the end of ozone therapy (approx. week 40).]
• Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at the end of ozone therapy). [Time frame: At the end of ozone therapy (approx. week 16).]
• Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at 12 weeks after the end of ozone therapy). [Time frame: At 12 weeks after the end of ozone therapy (approx. week 28).]
• Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at 24 weeks after the end of ozone therapy). [Time frame: At 24 weeks after the end of ozone therapy (approx. week 40).]
• Change from Baseline in Pain Score (Visual Analog Scale), (at the end of ozone therapy). [Time frame: At the end of ozone therapy (approx. week 16).]

Eligibility criteria

Inclusion criteria

• 1\. Adults ≥ 18 years old.
• 2\. Patients referred to the Chronic Pain Unit of the Dr. Negrín University Hospital for symptomatic/palliative treatment with ozone therapy because conventional treatment does not exist, has failed, has offered insufficient results, or is associated with high risk/morbidity.
• 3\. After evaluation of symptoms and patients, it exists a potential benefit of adding ozone treatment to the current treatment.
• 4\. Patients have no contraindications for ozone treatment.
• 5\. Patients must sign the specific Informed Consent for this study and for the ozone treatment.

Exclusion criteria

• 1\. Age < 18 years old.
• 2\. Psychiatric illness or social situations that would limit compliance with study requirements.

Contraindication or disability to attend scheduled treatments.

• 3\. Contraindication or disability to attend scheduled treatments.
• 4\. Uncontrolled clinical conditions (e.g., severe heart failure, massive hemorrhage, status epilepticus).
• 5\. Life expectancy < 6 months.
• 6\. Known allergy to ozone.
• 7\. Hemochromatosis (for systemic ozone treatment).
• 8\. Pregnancy (for systemic ozone treatment).
• 9\. Significant Glucose-6-Phosphate Dehydrogenase deficiency (Favism) (for systemic ozone treatment).
• 10\. Patients who do not meet the inclusion criteria.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

Spain · 1 center

• Dr. Negrín University Hospital — Las Palmas de Gran Canaria

Publications

• Clavo B, Cordoba-Lanus E, Martinez-Sanchez G, Federico M, Canovas-Molina A, Pinero JE, Vargas-Prado AM, Ramchandani A, Zajac M, Ribeiro I, Navarro M, Jorge IJ, Gonzalez-Martin JM, Martin-Alfaro R, Fernandez-Tagarro M, Diaz-Garrido JA, Lorenzo-Morales J, Rodriguez-Esparragon F. Modulating the Gut Microbiota via Rectal Ozone Insufflation in Gynecological Cancer Patients with Radiotherapy/Chemotherap PMID 41303051
• Clavo B, Canovas-Molina A, Federico M, Martinez-Sanchez G, Benitez G, Galvan S, Ramallo-Farina Y, Fabelo H, Cazorla-Rivero S, Lago-Moreno E, Antonilli C, Diaz-Garrido JA, Jorge IJ, Marrero-Callico G, Rodriguez-Abreu D, Rodriguez-Esparragon F. Ozone Treatment in the Management of Chemotherapy-Induced Peripheral Neuropathy: A Review of Rationale and Research Directions. Cancers (Basel). 2025 Jul 8;1 PMID 40723162
• Bisshopp S, Linertova R, Carames MA, Szolna A, Jorge IJ, Navarro M, Melchiorsen B, Rodriguez-Diaz B, Gonzalez-Martin JM, Clavo B. Pain Relief, Disability, and Hospital Costs After Intradiscal Ozone Treatment or Microdiscectomy for Lumbar Disc Herniation: A 24-Month Real-World Prospective Study. J Clin Med. 2025 Jun 26;14(13):4534. doi: 10.3390/jcm14134534. PMID 40648907
• Clavo B, Canovas-Molina A, Garcia-Lourve C, Cazorla-Rivero S, Federico M, Rodriguez-Esparragon F. Effects of ozone treatment on chemotherapy-induced peripheral neuropathy: a promising research area. Med Gas Res. 2025 Jun 1;15(2):195-197. doi: 10.4103/mgr.MEDGASRES-D-24-00074. Epub 2025 Jan 18. No abstract available. PMID 40070187
• Clavo B, Rodriguez-Abreu D, Galvan-Ruiz S, Federico M, Canovas-Molina A, Ramallo-Farina Y, Antonilli C, Benitez G, Fabelo H, Garcia-Lourve C, Gonzalez-Beltran D, Jorge IJ, Rodriguez-Esparragon F, Callico GM. Long-Term Effects of Ozone Treatment in Patients with Persistent Numbness and Tingling Secondary to Chemotherapy-Induced Peripheral Neuropathy. A Retrospective Study. Integr Cancer Ther. 2025 PMID 39797612
• Clavo B, Canovas-Molina A, Diaz-Garrido JA, Canas S, Ramallo-Farina Y, Laffite H, Federico M, Rodriguez-Abreu D, Galvan S, Garcia-Lourve C, Gonzalez-Beltran D, Carames MA, Hernandez-Fleta JL, Serrano-Aguilar P, Rodriguez-Esparragon F. Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study. Front Psychol. 2023 Aug 4;14:1176204. doi: PMID 37599784
• Clavo B, Rodriguez-Abreu D, Galvan S, Federico M, Martinez-Sanchez G, Ramallo-Farina Y, Antonelli C, Benitez G, Rey-Baltar D, Jorge IJ, Rodriguez-Esparragon F, Serrano-Aguilar P. Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report. Front Physiol. 2022 Aug 30;13:935269. doi: 10.3389/fphys.2022.935269. eCollection 202 PMID 36111149
• Clavo B, Canovas-Molina A, Ramallo-Farina Y, Federico M, Rodriguez-Abreu D, Galvan S, Ribeiro I, Marques da Silva SC, Navarro M, Gonzalez-Beltran D, Diaz-Garrido JA, Cazorla-Rivero S, Rodriguez-Esparragon F, Serrano-Aguilar P. Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors. Int J Environ Res Public PMID 36674232

Identifiers

NCT: NCT07325851 · 2025-642-1 · 0177-2025-OBS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗