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

NCT07325851 | Not Yet Recruiting

• 2 other identifiers: 2025-642-10177-2025-OBS
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chemotherapy-Induced Peripheral Neuropathy; Radiation Toxicity; Chronic Pain; Delayed Wound Healing; Refractory Symptoms

Keywords

Ozone Therapy; Health-related quality of life; Chemotherapy-induced Peripheral Neuropathy; Radiation-induced toxicity; Hyperspectral imaging; Infrared imaging; Heart Rate Variability; Sudoscan; Vibrometry; Oxidative stress; Gut Microbiota; Anxiety and Depression

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Health-Related Quality of Life by the "EQ-5D-5L" Questionnaire (at the end of ozone therapy).

  Self-reported evaluation of 5 physical and emotional items scored in five levels, plus a Visual Analog Scale (EQ-VAS) from 0 (worst health) to 100 (best health).

  At the end of ozone therapy (approx. week 16).

Secondary Outcomes (31)

• Change from Baseline in Health-Related Quality of Life by the "EQ-5D-5L" Questionnaire (at 12 weeks after the end of ozone therapy).

  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).

  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).

  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).

  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).

  At 24 week after the end of ozone therapy (approx. week 40).

Study Arms (1)

Ozone Group

Patients with refractory symptoms referred for palliative treatment with ozone therapy between 2026 and 2029.

Procedure: Ozone Therapy

Interventions

Ozone Therapy PROCEDURE

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.

Also known as: Ozone Treatment

Ozone Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients submitted to the Chronic Pain Unit of the Hospital Universitario de Gran Canaria Dr. Negrín, between January 2026 and December 2029, for symptomatic/palliative treatment with ozone therapy because standard treatment does not exist, it has been unsuccessful, or it is associated with high risk or high morbidity.

You may qualify if:

• \. Adults ≥ 18 years old.
• \. 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.
• \. After evaluation of symptoms and patients, it exists a potential benefit of adding ozone treatment to the current treatment.
• \. Patients have no contraindications for ozone treatment.
• \. Patients must sign the specific Informed Consent for this study and for the ozone treatment.

You may not qualify if:

• \. Age \< 18 years old.
• \. Psychiatric illness or social situations that would limit compliance with study requirements.
• Contraindication or disability to attend scheduled treatments.
• \. Contraindication or disability to attend scheduled treatments.
• \. Uncontrolled clinical conditions (e.g., severe heart failure, massive hemorrhage, status epilepticus).
• \. Life expectancy \< 6 months.
• \. Known allergy to ozone.
• \. Hemochromatosis (for systemic ozone treatment).
• \. Pregnancy (for systemic ozone treatment).
• \. Significant Glucose-6-Phosphate Dehydrogenase deficiency (Favism) (for systemic ozone treatment).

Sponsors & Collaborators

• Bernardino Clavo, MD, PhD: lead
• Dr. Negrin University Hospital: collaborator
• Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias: collaborator
• Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI): collaborator
• Instituto Universitario de Microelectrónica Aplicada de la Universidad de Las Palmas de Gran Canaria (IUMA-ULPGC): collaborator
• Council of Gran Canaria: collaborator

Study Sites (1)

Dr. Negrín University Hospital

Las Palmas de Gran Canaria, Las Palmas, 35019, Spain

Location

Related Publications (18)

• 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/Chemotherapy-Induced Pelvic Toxicity: A Proposed Clinical Study Protocol. J Clin Med. 2025 Nov 12;14(22):8015. doi: 10.3390/jcm14228015.

  PMID: 41303051 RESULT

• 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;17(14):2278. doi: 10.3390/cancers17142278.

  PMID: 40723162 RESULT

• 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 RESULT

• 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 RESULT

• 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 Jan-Dec;24:15347354241307038. doi: 10.1177/15347354241307038.

  PMID: 39797612 RESULT

• 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: 10.3389/fpsyg.2023.1176204. eCollection 2023.

  PMID: 37599784 RESULT

• 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 2022.

  PMID: 36111149 RESULT

• 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 Health. 2023 Jan 13;20(2):1479. doi: 10.3390/ijerph20021479.

  PMID: 36674232 RESULT

• Clavo B, Gutierrez D, Martin D, Suarez G, Hernandez MA, Robaina F. Intravesical ozone therapy for progressive radiation-induced hematuria. J Altern Complement Med. 2005 Jun;11(3):539-41. doi: 10.1089/acm.2005.11.539.

  PMID: 15992242 RESULT

• Clavo B, Suarez G, Aguilar Y, Gutierrez D, Ponce P, Cubero A, Robaina F, Carreras JL. Brain ischemia and hypometabolism treated by ozone therapy. Forsch Komplementmed. 2011;18(5):283-7. doi: 10.1159/000333795. Epub 2011 Oct 13.

  PMID: 22105041 RESULT

• Clavo B, Ceballos D, Gutierrez D, Rovira G, Suarez G, Lopez L, Pinar B, Cabezon A, Morales V, Oliva E, Fiuza D, Santana-Rodriguez N. Long-term control of refractory hemorrhagic radiation proctitis with ozone therapy. J Pain Symptom Manage. 2013 Jul;46(1):106-12. doi: 10.1016/j.jpainsymman.2012.06.017. Epub 2012 Oct 26.

  PMID: 23102757 RESULT

• Clavo B, Santana-Rodriguez N, Gutierrez D, Lopez JC, Suarez G, Lopez L, Robaina F, Bocci V. Long-term improvement in refractory headache following ozone therapy. J Altern Complement Med. 2013 May;19(5):453-8. doi: 10.1089/acm.2012.0273. Epub 2012 Dec 7.

  PMID: 23215625 RESULT

• Clavo B, Santana-Rodriguez N, Llontop P, Gutierrez D, Ceballos D, Mendez C, Rovira G, Suarez G, Rey-Baltar D, Garcia-Cabrera L, Martinez-Sanchez G, Fiuza D. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients. Evid Based Complement Alternat Med. 2015;2015:480369. doi: 10.1155/2015/480369. Epub 2015 Aug 18.

  PMID: 26357522 RESULT

• Clavo B, Santana-Rodriguez N, Llontop P, Gutierrez D, Suarez G, Lopez L, Rovira G, Martinez-Sanchez G, Gonzalez E, Jorge IJ, Perera C, Blanco J, Rodriguez-Esparragon F. Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted? Evid Based Complement Alternat Med. 2018 Sep 9;2018:7931849. doi: 10.1155/2018/7931849. eCollection 2018.

  PMID: 30271455 RESULT

• Clavo B, Rodriguez-Esparragon F, Rodriguez-Abreu D, Martinez-Sanchez G, Llontop P, Aguiar-Bujanda D, Fernandez-Perez L, Santana-Rodriguez N. Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects. Antioxidants (Basel). 2019 Nov 26;8(12):588. doi: 10.3390/antiox8120588.

  PMID: 31779159 RESULT

• Clavo B, Navarro M, Federico M, Borrelli E, Jorge IJ, Ribeiro I, Rodriguez-Melcon JI, Carames MA, Santana-Rodriguez N, Rodriguez-Esparragon F. Ozone Therapy in Refractory Pelvic Pain Syndromes Secondary to Cancer Treatment: A New Approach Warranting Exploration. J Palliat Med. 2021 Jan;24(1):97-102. doi: 10.1089/jpm.2019.0597. Epub 2020 May 5.

  PMID: 32379556 RESULT

• Clavo B, Navarro M, Federico M, Borrelli E, Jorge IJ, Ribeiro I, Rodriguez-Melcon JI, Carames MA, Santana-Rodriguez N, Rodriguez-Esparragon F. Long-Term Results with Adjuvant Ozone Therapy in the Management of Chronic Pelvic Pain Secondary to Cancer Treatment. Pain Med. 2021 Sep 8;22(9):2138-2141. doi: 10.1093/pm/pnaa459. No abstract available.

  PMID: 33738491 RESULT

• Clavo B, Martinez-Sanchez G, Rodriguez-Esparragon F, Rodriguez-Abreu D, Galvan S, Aguiar-Bujanda D, Diaz-Garrido JA, Canas S, Torres-Mata LB, Fabelo H, Tellez T, Santana-Rodriguez N, Fernandez-Perez L, Marrero-Callico G. Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial. Int J Mol Sci. 2021 Mar 10;22(6):2802. doi: 10.3390/ijms22062802.

  PMID: 33802143 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood and stool samples

MeSH Terms

Conditions

Radiation Injuries; Chronic Pain; Anxiety Disorders; Depression

Condition Hierarchy (Ancestors)

Wounds and Injuries; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Bernardino Clavo, MD, PhD

  Dr. Negrín University Hospital, Las Palmas, Spain

  STUDY CHAIR

• Francisco Rodríguez-Esparragón, BSc, PhyD

  Dr. Negrín University Hospital, Las Palmas, Spain

  PRINCIPAL INVESTIGATOR

• Ángeles Cánovas-Molina, RN

  Dr. Negrín University Hospital, Las Palmas, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernardino Clavo, MD, PhD.

CONTACT

+34 928449278; bernardinoclavo@gmail.com

Francisco Rodríguez-Esparragón, BSc, PhyD

CONTACT

+34 928449288; afrodesp@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 40 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Research Unit Director

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 8, 2026
• Study Start: January 14, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: January 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be available after publication, ending 36 months following article publication.
• Access Criteria: They will be available for investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.

Locations

ES (1)