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

NCT ID: NCT07259681

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

38 participants

Study Classification

OBSERVATIONAL

Study Start Date

2026-01-15

Study Completion Date

2028-03-31

Brief Summary

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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.

Detailed Description

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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

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

Keywords

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

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Adult women (\>=18 years).
2. Diagnosed with gynecological tumors (any location and stage).
3. Previously treated with radiotherapy and/or chemotherapy.
4. Must accept and sign the specific informed consent for this study.

5. Must present chronic TPIRQT with \>= 3 months of duration after habitual symptomatic treatment.
6. Must have a toxicity Grade of 2 (moderate symptoms, limiting instrumental ADL) or higher, according to the CTCAE v.5.0 scale.

2. 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.
3. 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.
4. Unwillingness or inability to provide written informed consent for study participation.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Dr. Negrin University Hospital

OTHER

Sponsor Role collaborator

Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI)

UNKNOWN

Sponsor Role collaborator

Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias

OTHER

Sponsor Role collaborator

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

UNKNOWN

Sponsor Role collaborator

CIBER (Infectious diseases)

UNKNOWN

Sponsor Role collaborator

Bernardino Clavo, MD, PhD

OTHER

Sponsor Role lead

Responsible Party

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Bernardino Clavo, MD, PhD

Principal Investigator, Research Unit Director

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Bernardino Clavo, MD, PhD

Role: STUDY_CHAIR

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

Jacob Lorenzo-Morales, Prof

Role: PRINCIPAL_INVESTIGATOR

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

Francisco Rodríguez-Esparragón, BSc, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Las Palmas de Gran Canaria, Las Palmas, Spain

Site Status

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

San Cristóbal de La Laguna, Tenerife, Spain

Site Status

Countries

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Spain

Central Contacts

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Bernardino Clavo, MD, PhD

Role: CONTACT

Phone: 34928449278

Email: [email protected]

Francisco Rodríguez-Esparragón, BSc, PhD

Role: CONTACT

Phone: 34928449288

Email: [email protected]

Facility Contacts

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Bernardino Clavo, MD, PhD

Role: primary

Francisco Rodríguez-Esparragón, BSc, PhD

Role: backup

Jacob Lorenzo-Morales, Prof

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 36674232 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33738491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32379556 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26357522 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23102757 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25955845 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34563216 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40618373 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40591053 (View on PubMed)

Other Identifiers

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PIFIISC25/52

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CIGC'25/26

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2025-436-1

Identifier Type: -

Identifier Source: org_study_id