Gut Microbiome in Gynecological Cancer Patients With Pelvic Toxicity: Controls Versus Ozone Treatment. (MicrOzoGineTox)

NCT07259681 | Not Yet Recruiting

• 3 other identifiers: 2025-436-1PIFIISC25/52CIGC'25/26
• Study Type: observational
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

Patients treated for gynecological tumors with radiotherapy (RT) and/or chemotherapy (CT) frequently develop pelvic toxicity (TPIRQT), a condition that can become persistent, progressive, and refractory to standard treatments. This toxicity, affecting the rectum (proctitis), bladder (cystitis), and vagina (mucositis), severely deteriorates quality of life. Standard options for refractory cases are limited; at our center, rectal ozone therapy is used with high rates of symptomatic improvement (66-75%). Emerging evidence suggests a link between gut microbiota and the development of TPIRQT. However, it is unknown how rectal ozone therapy may influence the gut microbiome or if this modulation is part of its therapeutic mechanism. This prospective observational study will investigate the potential relationship between gut microbiome profiles (composition and diversity), the presence and severity of TPIRQT, and the response to rectal ozone therapy.

Conditions

Chemotherapy Toxicity; Gynecological Tumors; Radiation Proctitis; Pelvic Toxicity; Radiation Toxicity; Radiation Cystitis; Vaginal Mucositis; Vulvar Mucositis; Quality of Life; Dysbiosis

Keywords

Gut microbiota; Ozone; Ozone therapy; Gynecological tumors; Radiotherapy; Chemotherapy; Side effects; Actinic proctitis; Actinic cystitis; Quality of life; Dysbiosis

Outcome Measures

Primary Outcomes (3)

• Comparison of gut microbiome profile (composition and diversity) between TPIRQT and Control groups

  Gut microbiome composition and diversity (from a single sample) in control patients will be compared to the baseline profile of patients with TPIRQT.

  Baseline (single time point for controls, pre-ozone for cases)

• Change in gut microbiome profile (composition and diversity) in patients with TPIRQT after rectal ozone therapy.

  Gut microbiome composition and diversity will be analyzed from stool samples using 16S ribosomal RNA gene sequencing.

  Baseline (pre-ozone therapy) , 4 Months (post-ozone therapy)

• Correlation of gut microbiome profile with grade of pelvic toxicity.

  Toxicity will be assessed using: i) the CTCAE v.5.0 scale from the NCI , and ii) the EORTC QLQ-CX24 questionnaire. This will be evaluated for its relationship to microbiome data.

  Baseline (for Control group); Baseline, 4 Months (for TPIRQT group).

Secondary Outcomes (3)

• Correlation of gut microbiome profile with health-related quality of life (HRQoL).

  Baseline (for Control group); Baseline, 4 Months (for TPIRQT group).

• Correlation of gut microbiome profile with anxiety and depression levels.

  Baseline (for Control group); Baseline, 4 Months (for TPIRQT group).

• Correlation of gut microbiome profile with biochemical markers of oxidative stress and inflammation.

  Baseline (for Control group); Baseline, 4 Months (for TPIRQT group).

Study Arms (2)

TPIRQT Group (Cases)

Patients with gynecological tumors treated with RT and/or CT who develop chronic pelvic toxicity (TPIRQT) and are referred for compassionate-use rectal ozone therapy at the Chronic Pain Unit. Samples and data will be collected before and after ozone therapy

Control Group

pelvic toxicity (TPIRQT). This group will be matched by age (± 5 years) and primary tumor location. Samples and data will be collected once during a follow-up visit.

Eligibility Criteria

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

Study Population

Patients with gynecological tumors treated with RT and/or CT with or without chronic pelvic toxicity (TPIRQT).

You may qualify if:

• Adult women (\>=18 years).
• Diagnosed with gynecological tumors (any location and stage).
• Previously treated with radiotherapy and/or chemotherapy.
• Must accept and sign the specific informed consent for this study.
• Must present chronic TPIRQT with \>= 3 months of duration after habitual symptomatic treatment.
• Must have a toxicity Grade of 2 (moderate symptoms, limiting instrumental ADL) or higher, according to the CTCAE v.5.0 scale.

You may not qualify if:

• Presence of active inflammatory bowel disease (e.g., Crohn's Disease, Ulcerative Colitis) or a history of major gastrointestinal resection (excluding appendectomy) that could significantly alter gut anatomy and microbiota.
• Any uncontrolled intercurrent illness or psychiatric condition that, in the investigator's opinion, would limit compliance with study requirements or interfere with the interpretation of results.
• Unwillingness or inability to provide written informed consent for study participation.

Sponsors & Collaborators

• Bernardino Clavo, MD, PhD: lead
• CIBER (Infectious diseases): collaborator
• Dr. Negrin University Hospital: collaborator
• Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI): collaborator
• Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias: collaborator
• Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna: collaborator

Study Sites (2)

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

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

Location

Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias - Universidad de La Laguna

San Cristóbal de La Laguna, Tenerife, 38296, Spain

Location

Related Publications (9)

• 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, 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, 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, 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 BACKGROUND

• Wang A, Ling Z, Yang Z, Kiela PR, Wang T, Wang C, Cao L, Geng F, Shen M, Ran X, Su Y, Cheng T, Wang J. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One. 2015 May 8;10(5):e0126312. doi: 10.1371/journal.pone.0126312. eCollection 2015.

  PMID: 25955845 BACKGROUND

• Wang L, Wang X, Zhang G, Ma Y, Zhang Q, Li Z, Ran J, Hou X, Geng Y, Yang Z, Feng S, Li C, Zhao X. The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review. Radiat Oncol. 2021 Sep 25;16(1):187. doi: 10.1186/s13014-021-01899-y.

  PMID: 34563216 BACKGROUND

• Li L, Yang Z, Yi Y, Song Y, Zhang W. Gut microbiota and radiation-induced injury: mechanistic insights and microbial therapies. Gut Microbes. 2025 Dec;17(1):2528429. doi: 10.1080/19490976.2025.2528429. Epub 2025 Jul 6.

  PMID: 40618373 BACKGROUND

• Ma CY, Zhao J, Xu XT, He XL, Qin SB, Zhou JY. Predictive biomarkers in the gut microbiome and metabolome for severe acute radiation enteritis in cervical cancer radiotherapy. Discov Oncol. 2025 Jul 1;16(1):1220. doi: 10.1007/s12672-025-03077-y.

  PMID: 40591053 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Stool and serum samples

MeSH Terms

Conditions

Radiation Injuries; Dysbiosis

Condition Hierarchy (Ancestors)

Wounds and Injuries; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bernardino Clavo, MD, PhD

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

  STUDY CHAIR

• Jacob Lorenzo-Morales, Prof

  Instituto Universitario de Enfermedades Tropicales y Salud Publica de Canarias, Universidad La Laguna

  PRINCIPAL INVESTIGATOR

• Francisco Rodríguez-Esparragón, BSc, 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
• Target Duration: 4 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Research Unit Director

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 2, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• 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 (2)