Gene and Molecular Pathways of Ozone Treatment Response in Gynecological Tumor Patients With Chronic Pelvic Pain Secondary to Cancer Treatment

NCT06816095 | Recruiting

• 3 other identifiers: 2024-192-1DISA'24: OA24/104CIGC'23/24
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Gynecological cancers, including those affecting the ovaries, uterus, and cervix, represent a significant health burden for women. While survival rates have improved, many women experience chronic pelvic pain secondary to cancer treatment, especially radiotherapy and chemotherapy. This treatment-induced pelvic pain can be of difficult management and significantly affects patients' quality of life. In our experience, ozone therapy has emerged as a promising complementary treatment for pain relief in patients with chronic diseases, including side effects of cancer treatment. However, the genetic and epigenetic mechanisms influencing its effectiveness have not yet been thoroughly studied. The aim of this prospective study is to analyze how ozone therapy modulates the expression of certain genes and its impact on epigenetic clocks, which could help predict pain response.

Conditions

Chronic Pelvic Pain Syndrome (CPPS); Radiation-Induced Disorder; Radiotherapy Side Effects; Side Effect of Chemotherapy; Gynecological Cancers

Keywords

Radiation-Induced Disorder; Radiotherapy Side Effects; Cancer survivors; Chronic Pelvic Pain Syndrome (CPPS); Gynecological Cancers; gene expression; epigenetic clocks; side effects of cancer treatment; Toxicity of chemotherapy; Ozone therapy; Quality of Life; oxidative stress

Outcome Measures

Primary Outcomes (4)

• Differences in gene expression among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy.

  Differences (among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy) in gene expression profile.

  At 0 week

• Changes (from baseline) in gene expression at the end of ozone treatment.

  Changes (from baseline) in gene expression profile, after ozone treatment.

  At 16 weeks

• Differences in biological age based on epigenetic clocks among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy

  Differences (among patients with or without chronic pain induced by radiotherapy/chemotherapy) in the biological age based on epigenetic clocks.

  At 0 week.

• Changes (from baseline) in the biological age based on epigenetic clocks, after ozone treatment

  Changes (from baseline) in the biological age based on epigenetic clocks, after ozone treatment

  At 16 weeks.

Secondary Outcomes (10)

• Differences in the grade of toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 scale among patients with or without chronic pain induced by radiotherapy/chemotherapy

  At 0 week.

• Changes (from baseline) in the grade of toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 scale, after ozone treatment.

  At 16 weeks.

• Differences in pain score according to the visual analog scale (VAS) among patients with or without chronic pain induced by radiotherapy/chemotherapy

  At 0 week.

• Change (from baseline) in pain score according to the visual analog scale (VAS), after ozone treatment.

  At 16 weeks.

• Differences in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients among patients with or without chronic pain induced by radiotherapy/chemotherapy.

  At 0 week.

Study Arms (2)

Treated patients, without secondary pain

Patients with gynecological tumors, treated with radiotherapy/chemotherapy, without chronic pelvic pain.

Treated patients, with chronic pelvic pain

Patients with gynecological tumors, treated with radiotherapy/chemotherapy, with chronic pelvic pain, submitted to our Chronic Pain Unit for compassionate/palliative ozone treatment.

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Adult women with female reproductive organs who are at risk for gynecological cancers
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult women (≥18 years) with gynecological tumors treated with radiotherapy-chemotherapy.

You may qualify if:

• Adult women (\>=18 years old) with gynecological tumors treated with radiotherapy-chemotherapy.
• Cancer disease is stable or in remission.
• Life expectancy \> = 6 months.
• Patients included in the group of patients with pelvic pain must have a clinical, radiological, endoscopic, or histopathological diagnosis that their pain is not secondary to the oncological process.
• Patients included in the group of patients with pelvic pain must have pain for \>= 3 months duration, with an intensity \>= 3 on the Visual Analog Scale (VAS), or classified as toxicity \>= Grade-2 of the CTCAE v.5.0 of the National Cancer Institute of the USA.
• Signed and dated informed consent specific to this study.

You may not qualify if:

• Age \< 18 years old.
• Severe psychiatric disorders.
• Inability to complete the quality of life questionnaires.
• Active neoplasia requiring recent initiation (\< 3 months) of systemic or local treatment.
• Life expectancy (for any reason) \< 6 months.

Sponsors & Collaborators

• Bernardino Clavo, MD, PhD: lead
• Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias: collaborator
• Fundación DISA, Canary Islands, Spain: collaborator
• Council of Gran Canaria: collaborator

Study Sites (1)

Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC)

Las Palmas, Las Palmas, 35019, Spain

RECRUITING

Related Publications (15)

• Tricarico G, Travagli V. The Relationship between Ozone and Human Blood in the Course of a Well-Controlled, Mild, and Transitory Oxidative Eustress. Antioxidants (Basel). 2021 Dec 4;10(12):1946. doi: 10.3390/antiox10121946.

  PMID: 34943049 BACKGROUND

• Hidalgo-Tallon FJ, Torres-Morera LM, Baeza-Noci J, Carrillo-Izquierdo MD, Pinto-Bonilla R. Updated Review on Ozone Therapy in Pain Medicine. Front Physiol. 2022 Feb 23;13:840623. doi: 10.3389/fphys.2022.840623. eCollection 2022.

  PMID: 35283802 BACKGROUND

• Galie M, Covi V, Tabaracci G, Malatesta M. The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure. Int J Mol Sci. 2019 Aug 17;20(16):4009. doi: 10.3390/ijms20164009.

  PMID: 31426459 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Bocci VA, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. J Transl Med. 2011 May 17;9:66. doi: 10.1186/1479-5876-9-66.

  PMID: 21575276 BACKGROUND

• Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015 Feb 2;3:4. doi: 10.3389/fchem.2015.00004. eCollection 2015.

  PMID: 25699252 BACKGROUND

• Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009 Jul;29(4):646-82. doi: 10.1002/med.20150.

  PMID: 19260079 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Abnormalities, Radiation-Induced

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Radiation Injuries; Wounds and Injuries

Study Officials

• Bernardino Clavo, MD, PhD

  Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.

  STUDY CHAIR

• Francisco Rodríguez-Esparragón, BSc, PhD

  Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.

  STUDY DIRECTOR

• Sara Cazorla-Rivero, BSc, PhD

  Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.

  PRINCIPAL INVESTIGATOR

• Mario Federico, MD, PhD

  Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bernardino Clavo, MD, PhD

CONTACT

34928449278; bernardinoclavo@gmail.com

Francisco Rodríguez-Esparragón, BSc, PhD

CONTACT

34928449288; afrodesp@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Research Unit

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 10, 2025
• Study Start: February 10, 2025
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): August 14, 2027
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available after publication, ending 36 months following article publication.
• Access Criteria: Data will be available for investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. \- Study protocol Proposals should be directed to: bernardinoclavo@gmail.com To gain access, data requestors will need to sign a data access agreement.

Locations

ES (1)