Chronic Pelvic Pain Syndrome (CPPS), Gynecological Cancers, Radiation-Induced Disorder, Radiotherapy Side Effects, Side Effect of Chemotherapy
Conditions
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
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
Interventions
None listed
Sponsors
Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias
Fundación DISA, Canary Islands, Spain
Council of Gran Canaria
Bernardino Clavo, MD, PhD
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in gene expression among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy. | At 0 week | Differences (among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy) in gene expression profile. |
| Changes (from baseline) in gene expression at the end of ozone treatment. | At 16 weeks | Changes (from baseline) in gene expression profile, after ozone treatment. |
| Differences in biological age based on epigenetic clocks among patients with or without chronic pelvic pain induced by radiotherapy/chemotherapy | At 0 week. | Differences (among patients with or without chronic pain induced by radiotherapy/chemotherapy) in the biological age based on epigenetic clocks. |
| Changes (from baseline) in the biological age based on epigenetic clocks, after ozone treatment | At 16 weeks. | Changes (from baseline) in the biological age based on epigenetic clocks, after ozone treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Changes (from baseline) in the grade of toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities in daily life). |
| 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. | Self-reported evaluation of the severity of pain according to the VAS, scored from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| Change (from baseline) in pain score according to the visual analog scale (VAS), after ozone treatment. | At 16 weeks. | Self-reported evaluation of the severity of pain according to the VAS, scored from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| Changes (from baseline) in biochemical parameters of oxidative stress, after ozone treatment. | At 16 weeks. | Changes in serum levels of antioxidants and free radicals. |
| Differences in biochemical parameters of inflammation among patients with or without chronic pain induced by radiotherapy/chemotherapy. | At 0 week. | Differences in serum levels of pro-inflammatory cytokines. |
| Changes (from baseline) in biochemical parameters of inflammation, after ozone treatment. | At 16 weeks. | Changes in serum levels of pro-inflammatory cytokines. |
| 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. | Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (Best: I have no problem) to 5 (worst: I have an extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analog scale (0 = worst health patient can imagine, 100 = best health patient can imagine). |
| Changes (from baseline) in Quality of Life (using the EQ-5D-5L questionnaire) self-perceived by patients, after ozone treatment. | At 16 weeks. | Self-reported evaluation of: a) 5 physical and emotional items scored in five levels, from 1 (Best: I have no problem) to 5 (worst: I have an extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analog scale (0 = worst health patient can imagine, 100 = best health patient can imagine). |
| Differences in biochemical parameters of oxidative stress among patients with or without chronic pain induced by radiotherapy/chemotherapy. | At 0 week. | Differences in serum levels of antioxidants and free radicals. |
| 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. | Differences (among patients with or without chronic pain induced by radiotherapy/chemotherapy) in the grade of toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities in daily life). |
Countries
Spain
Contacts
Primary ContactBernardino Clavo, MD, PhD
Backup ContactFrancisco Rodríguez-Esparragón, BSc, PhD
Outcome results
None listed