Clinical trial NCT06816095: Gene and Molecular Pathways of Ozone Treatment Response in Gynecological Tumor Patients With Chronic Pelvic Pain Secondary to Cancer Treatment
Official title: Gene and Molecular Pathway Characterization of the Response to Ozone Treatment in Gynecological Tumor Patients With Chronic Pelvic Pain Secondary to Radio-chemotherapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Dr. Negrin University Hospital
Sponsor class: OTHER
Collaborators: name: Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias
name: Fundación DISA, Canary Islands, Spain
name: Council of Gran Canaria
First posted: 2025-02-10
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult women (≥18 years) with gynecological tumors treated with radiotherapy-chemotherapy.

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.

Detailed description: While survival rates of gynecological cancers have improved, many women experience chronic pelvic pain as a consequence of cancer treatment, particularly radiotherapy and chemotherapy. This persistent pain often has neuropathic characteristics, and it can be challenging to manage, negatively impacting physical and emotional well-being and quality of life.

Conventional pain management strategies for these patients often provide limited relief. In our experience, ozone therapy has emerged as a promising option for managing chronic pain in various conditions, including side effects of cancer treatment.

While the clinical benefits of ozone therapy have been observed in preliminary studies, the underlying molecular mechanisms underlying its analgesic effect remain largely unknown. Understanding how ozone therapy influences gene expression and epigenetic modifications could facilitate the identification of genes involved in the differential response to ozone therapy and a potential way for personalized strategies for pain treatment.

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.

Primary Objectives:

In patients with gynecological tumors treated by radiotherapy/chemotherapy, To evaluate

* among patients with or without chronic pelvic pain induced by treatment.
* before and after ozone treatment in those patients treated because of pelvic pain induced by radiotherapy/chemotherapy.

The potential differences in:

1. Gene expression.
2. Biological age based on epigenetic clocks:

Secondary Objectives:

Evaluate in those patients the potential relationship between gene expression and epigenetic clocks with:

1. Grade of toxicity
2. Pain score
3. Health-related quality of life,
4. Biochemical markers of oxidative stress and inflammation.

Trial Design:

This observational and prospective study will analyze data from two groups of patients with gynecological tumors treated with radiotherapy/chemotherapy:

* A group of patients with chronic pelvic pain secondary to radiotherapy-chemotherapy, submitted to our Chronic Pain Unit for compassionate/palliative ozone treatment.
* A group of patients without secondary chronic pelvic pain.

Trial Population:

Adult women (≥ 18 years old) with gynecological tumors treated with radiotherapy-chemotherapy. They will be analyzed into two different groups of patients:

* A group of patients with chronic pelvic pain secondary to radiotherapy-chemotherapy, submitted to our Chronic Pain Unit for compassionate/palliative ozone treatment.
* A group of patients without secondary chronic pelvic pain.

Intervention. No intervention. The management of patients will be the standard of care in our hospital.

Study Duration:

The primary completion date is planned for 14/February/2027. The study completion date is planned for 14/August/2027

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Failure to meet all inclusion criteria

Primary outcomes:
measure: Differences in gene expression among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy.
timeFrame: At 0 week
measure: Changes (from baseline) in gene expression at the end of ozone treatment.
timeFrame: At 16 weeks
measure: Differences in biological age based on epigenetic clocks among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy
timeFrame: At 0 week.
measure: Changes (from baseline) in the biological age based on epigenetic clocks, after ozone treatment
timeFrame: At 16 weeks.
Secondary outcomes:
measure: 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
timeFrame: At 0 week.
measure: 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.
timeFrame: At 16 weeks.
measure: Differences in pain score according to the visual analog scale (VAS) among patients with or without chronic pain induced by radiotherapy/chemotherapy
timeFrame: At 0 week.
measure: Change (from baseline) in pain score according to the visual analog scale (VAS), after ozone treatment.
timeFrame: At 16 weeks.
measure: 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.
timeFrame: At 0 week.
measure: Changes (from baseline) in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients, after ozone treatment.
timeFrame: At 16 weeks.
measure: Differences in biochemical parameters of oxidative stress among patients with or without chronic pain induced by radiotherapy/chemotherapy.
timeFrame: At 0 week.
measure: Changes (from baseline) in biochemical parameters of oxidative stress, after ozone treatment.
timeFrame: At 16 weeks.
measure: Differences in biochemical parameters of inflammation among patients with or without chronic pain induced by radiotherapy/chemotherapy.
timeFrame: At 0 week.
measure: Changes (from baseline) in biochemical parameters of inflammation, after ozone treatment.
timeFrame: At 16 weeks.
Other outcomes:
Locations:
city: Las Palmas
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC)
Study officials:
affiliation: Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.
name: Bernardino Clavo, MD, PhD
role: STUDY_CHAIR
affiliation: Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.
name: Francisco Rodríguez-Esparragón, BSc, PhD
role: STUDY_DIRECTOR
affiliation: Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.
name: Sara Cazorla-Rivero, BSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain.
name: Mario Federico, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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