Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2022 and 2025

Study Overview
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Brief Summary
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The main objective of this study is to analyze the impact on the health-related quality of life of patients with refractory symptoms, who have been referred to the HUGCDN Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between June-2022 and December-2025

Detailed Description
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Chronic Pain Unit in the absence or failure of standard treatment, or when the standard treatment is associated with high morbidity or high risk. Frequently, these patients present alterations in self-perceived health-related quality of life (HRQoL), anxiety, depression, and other symptoms. This study aims to evaluate in these patients the effect of adjuvant symptomatic/palliative ozone therapy on the HRQoL and the potential changes from baseline on several parameters after treatment. MAIN OBJECTIVES: To evaluate in these patients: 1) the clinical effect on the HRQOL of adding ozone to the standard treatment. SECONDARY OBJECTIVES: To evaluate in these patients changes from baseline on 2) anxiety and depression, 3) pain (if applicable), 4) grade of toxicity (if applicable), 5) requirements of invasive procedures for symptom management, 6) evolution of main symptoms, 7) evolution of oxidative stress and inflammation (if systemic ozone therapy). METHODOLOGY: Prospective and observational study of patients referred to our Chronic Pain Unit for symptomatic/palliative treatment with ozone therapy between 2022 and 2025. MAIN VARIABLE: 1) HRQoL through the EQ-5D-5L questionnaire SECONDARY VARIABLE: 2) anxiety and depression through the hospital anxiety/depression (HAD) questionnaire, 3) Pain through the visual analog scale (VAS), 4) grade of toxicity in cancer patients through the CTCAE v5.0 scale, 5) the number of invasive procedures required for symptom management, 6) self -reported percentage of symptom improvement, 7) biochemical parameters of oxidative stress and inflammation. Assessments at weeks: 0 (baseline), 16 (end of O3/O2 treatment, objective), 28 (12 weeks after the end of ozone), and 40 (24 weeks after the end of ozone, control) Length of treatment: as required; initially, planned 16 weeks. Follow-up: 24 weeks after finishing O3/O2 treatment. Planned length of the clinical trial: 49 months.

Official Title
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Prospective and Observational Study of Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2022 and 2025. (EPOOzo)

Conditions
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Refractory Pain, Radiation Toxicity, Chemotherapeutic Toxicity, Chemotherapy-induced Peripheral Neuropathy, Delayed Wound Healing, Chronic Pain

Intervention / Treatment
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* Other: Ozone therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults > = 18 years old. Patients submitted to the Chronic Pain Unit of the Hospital Universitario de Gran Canaria Dr. Negrín for symptomatic/palliative treatment with ozone therapy because conventional treatment does not exist, it has been unsuccessful, or it is associated with high risk or high morbidity. After evaluation of symptoms and patients, it exists a potential benefit of adding ozone treatment to the current treatment. Patients have no contraindications for ozone treatment. Patients have signed and dated the informed consent for the compassionated ozone treatment and the specific informed consent for this study Exclusion Criteria: Age < 18 years old. Psychiatric illness or social situations that would limit compliance with study requirements. Those who are incapable to fill in the scales used to measure variables. Hemodynamically or clinically unstable patients or uncontrolled severe illness. Uncontrolled cancer disease requiring chemotherapy treatment. Life expectancy < 6 months Contraindication or disability or to attend scheduled treatments. Known allergy to ozone. Pregnancy at the time of enrollment (for systemic ozone therapy). 10 Hemochromatosis (for systemic ozone therapy). 11. Known significant glucose-6-phosphate dehydrogenase deficiency (favism, acute hemolytic anemia) (for systemic ozone therapy). 12. Patients who do not meet all the inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ozone group<br>Patients treated with ozone as adjuvant palliative therapy. The procedure of ozone administration, dosage, frequency, and duration of ozone treatment will depend on the treated symptom and clinical evolution. Usually planned 40 sessions. | Other: Ozone therapy<br>* Systemic and/or local ozone administration. Dosage, frequency, and duration of ozone treatment will depend on the treated symptom and clinical evolution. Usually planned 40 sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the health-related quality of life by the 5-level, 5-dimension EuroQol (EQ-5D-5L) questionnaire (at the end of ozone therapy) | 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 extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale (at the end of ozone therapy) | HAD scale is a self-administered questionnaire which assesses 14 items pertaining to symptoms of anxiety (seven) and depression (seven) experienced by patients. Each item is scored from 0 (better, no alteration) to 3 (worse level of alteration). For each symptom, overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression). | 16 weeks | 
| Change from Baseline in pain score according to the visual analog scale (VAS) (at the end of ozone therapy) | 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) | 16 weeks | 
| Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale (at the end of ozone therapy) | Grade of toxicity secondary to cancer-treatment according to the CTCAE v5.0 (Common Terminology Criteria for Adverse Events from the National Cancer Institute) scale. Each toxicity is usually scored from 0 (asymptomatic or mild symptoms) to 5 (death). | 16 weeks | 
| Changes from Baseline in requirements of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management (at the end of ozone therapy) | Number of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management. | 16 weeks | 
| Changes from Baseline in the main symptoms (at the end of ozone therapy) | Self -reported percentage of symptom improvement from Baseline | 16 weeks | 
| Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy) (at the end of ozone therapy). | Serum levels of biochemical parameters of oxidative stress | 16 weeks | 
| Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy) (at the end of of ozone therapy). | Serum levels of pro-inflammatory cytokines | 16 weeks | 
| Change from Baseline in the health-related quality of life by the 5-level, 5-dimension EuroQol (EQ-5D-5L) questionnaire. | 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 extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine) | 28 weeks | 
| Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale. | HAD scale is a self-administered questionnaire which assesses 14 items pertaining to symptoms of anxiety (seven) and depression (seven) experienced by patients. Each item is scored from 0 (better, no alteration) to 3 (worse level of alteration). For each symptom, overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression). | 28 weeks | 
| Change from Baseline in pain score according to the visual analog scale (VAS). | 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) | 28 weeks | 
| Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale. | Grade of toxicity secondary to cancer-treatment according to the CTCAE v5.0 (Common Terminology Criteria for Adverse Events from the National Cancer Institute) scale. Each toxicity is usually scored from 0 (asymptomatic or mild symptoms) to 5 (death). | 28 weeks | 
| Changes from Baseline in requirements of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management. | Number of invasive procedures ((surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management. | 28 weeks | 
| Changes from Baseline in the main symptoms. | Self -reported percentage of symptom improvement from Baseline | 28 weeks | 
| Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy). | Serum levels of biochemical parameters of oxidative stress | 28 weeks | 
| Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy). | Serum levels of pro-inflammatory cytokines | 28 weeks | 
| Change from Baseline in the health-related quality of life by the 5-level, 5-dimension EuroQol (EQ-5D-5L) questionnaire. | 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 extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine) | 40 weeks | 
| Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale. | HAD scale is a self-administered questionnaire which assesses 14 items pertaining to symptoms of anxiety (seven) and depression (seven) experienced by patients. Each item is scored from 0 (better, no alteration) to 3 (worse level of alteration). For each symptom, overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression). | 40 weeks | 
| Change from Baseline in pain score according to the visual analog scale (VAS). | 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) | 40 weeks | 
| Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale. | Grade of toxicity secondary to cancer-treatment according to the CTCAE v5.0 (Common Terminology Criteria for Adverse Events from the National Cancer Institute) scale. Each toxicity is usually scored from 0 (asymptomatic or mild symptoms) to 5 (death). | 40 weeks | 
| Changes from Baseline in requirements of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management. | Number of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management. | 40 weeks | 
| Changes from Baseline in the main symptoms. | Self -reported percentage of symptom improvement from Baseline | 40 weeks | 
| Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy). | Serum levels of biochemical parameters of oxidative stress | 40 weeks | 
| Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy). | Serum levels of pro-inflammatory cytokines | 40 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy-induced Peripheral Neuropathy, Radiation-induced toxicity, Cancer-treatment side effects, Delayed wound healing, Chronic pain, Health-related quality of life, Anxiety and Depression, Ozone therapy, Refractory pain