Chemotherapy-Induced Peripheral Neuropathy, Chronic Pain, Delayed Wound Healing, Radiation Toxicity, Refractory Symptoms
Conditions
Keywords
Ozone Therapy, Health-related quality of life, Chemotherapy-induced Peripheral Neuropathy, Radiation-induced toxicity, Hyperspectral imaging, Infrared imaging, Heart Rate Variability, Sudoscan, Vibrometry, Oxidative stress, Gut Microbiota, Anxiety and Depression
Brief summary
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 Dr. Negrín University Hospital Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between January 2026 and December 2029. Additionally, the study aims to evaluate several specific symptoms, hyperspectral and thermal images, non-invasive clinical parameters related to the Autonomic Nervous System (such as heart rate variability, electrochemical skin conductance, and vibration perception thresholds), oxidative stress and inflammatory parameters, and gut microbiota composition.
Detailed description
Patients are referred to the 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 such as radiation-induced pelvic toxicity or chemotherapy-induced peripheral neuropathy (CIPN). This prospective observational study (EPOOzo-2) aims to evaluate the effect of adjuvant symptomatic/palliative ozone therapy on HRQoL and potential changes from baseline. Specifically, it incorporates new non-invasive technologies to objectively assess microcirculation, neuropathy and autonomic regulation. Main Objectives: 1\. Analyze the impact on HRQoL of patients with refractory symptoms treated with ozone. Secondary Objectives: Depending on the clinical case, analyze the impact of ozone treatment on: 2. Anxiety and depression. 3. Treated symptoms (e.g., pain, paresthesia). 4. Fatigue. 5. Toxicity grade (in cancer patients). 6. Non-invasive clinical parameters related to the Autonomic Nervous System (central and peripheral) and somatosensory function. 7. Biochemical parameters and gut microbiome analysis (in patients with systemic/rectal ozone). Methodology: Prospective and observational study of patients referred for symptomatic/palliative ozone therapy between January 2026 and December 2029. Assessments at weeks: 0 (baseline), 16 (end of O3/O2 treatment), 28 (12 weeks after the end of ozone), and 40 (24 weeks after the end of ozone).
Interventions
PROCEDUREOzone Therapy
Systemic (rectal, autohemotherapy) and/or local ozone administration (cutaneous, intravaginal, intravesical). Dosage, frequency, and duration will depend on the symptoms treated and clinical evolution. Usually planned 40 sessions over 4 months.
Sponsors
Dr. Negrin University Hospital
Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias
Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI)
Instituto Universitario de Microelectrónica Aplicada de la Universidad de Las Palmas de Gran Canaria (IUMA-ULPGC)
Council of Gran Canaria
Bernardino Clavo, MD, PhD
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Adults ≥ 18 years old. * 2\. Patients referred to the Chronic Pain Unit of the Dr. Negrín University Hospital for symptomatic/palliative treatment with ozone therapy because conventional treatment does not exist, has failed, has offered insufficient results, or is associated with high risk/morbidity. * 3\. After evaluation of symptoms and patients, it exists a potential benefit of adding ozone treatment to the current treatment. * 4\. Patients have no contraindications for ozone treatment. * 5\. Patients must sign the specific Informed Consent for this study and for the ozone treatment.
Exclusion criteria
* 1\. Age \< 18 years old. * 2\. Psychiatric illness or social situations that would limit compliance with study requirements. Contraindication or disability to attend scheduled treatments. * 3\. Contraindication or disability to attend scheduled treatments. * 4\. Uncontrolled clinical conditions (e.g., severe heart failure, massive hemorrhage, status epilepticus). * 5\. Life expectancy \< 6 months. * 6\. Known allergy to ozone. * 7\. Hemochromatosis (for systemic ozone treatment). * 8\. Pregnancy (for systemic ozone treatment). * 9\. Significant Glucose-6-Phosphate Dehydrogenase deficiency (Favism) (for systemic ozone treatment). * 10\. Patients who do not meet the inclusion criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Health-Related Quality of Life by the EQ-5D-5L Questionnaire (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Self-reported evaluation of 5 physical and emotional items scored in five levels, plus a Visual Analog Scale (EQ-VAS) from 0 (worst health) to 100 (best health). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Health-Related Quality of Life by the EQ-5D-5L Questionnaire (at 24 weeks after the end of ozone therapy). | At 24 weeks after the end of ozone therapy (approx. week 40). | Self-reported evaluation of 5 physical and emotional items scored in five levels, plus a Visual Analog Scale (EQ-VAS) from 0 (worst health) to 100 (best health). |
| Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Hospital Anxiety and Depression Scale (HADS). Scores range from 0 to 21 for each subscale, where higher scores indicate worse anxiety or depression. |
| Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at 12 weeks after the end of ozone therapy). | At 12 week after the end of ozone therapy (approx. week 28). | Hospital Anxiety and Depression Scale (HADS). Scores range from 0 to 21 for each subscale, where higher scores indicate worse anxiety or depression. |
| Change from Baseline in Anxiety and Depression Levels (HAD Scale) (at 24 weeks after the end of ozone therapy). | At 24 week after the end of ozone therapy (approx. week 40). | Hospital Anxiety and Depression Scale (HADS). Scores range from 0 to 21 for each subscale, where higher scores indicate worse anxiety or depression. |
| Change from Baseline in Health-Related Quality of Life by the QLQ-C30 Questionnaire (only in cancer patients). (At the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | The EORTC QLQ-C30 is a 30-item questionnaire that includes five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status scale, and several single items. Scores are transformed to a 0-100 scale. For functional and global health scales, higher scores represent better functioning or quality of life. For symptom scales/items, higher scores indicate greater symptomatology or problems |
| Change from Baseline in Health-Related Quality of Life by the QLQ-C30 Questionnaire (only in cancer patients). (At 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | The EORTC QLQ-C30 is a 30-item questionnaire that includes five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status scale, and several single items. Scores are transformed to a 0-100 scale. For functional and global health scales, higher scores represent better functioning or quality of life. For symptom scales/items, higher scores indicate greater symptomatology or problems |
| Change from Baseline in Health-Related Quality of Life by the QLQ-C30 Questionnaire (only in cancer patients). (At 24 weeks after the end of ozone therapy). | At 24 weeks after the end of ozone therapy (approx. week 40). | The EORTC QLQ-C30 is a 30-item questionnaire that includes five functional scales (physical, role, emotional, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status scale, and several single items. Scores are transformed to a 0-100 scale. For functional and global health scales, higher scores represent better functioning or quality of life. For symptom scales/items, higher scores indicate greater symptomatology or problems |
| Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Assessed using the Chalder Fatigue Scale (CFQ-11) and/or EORTC QLQ-FA12 for cancer patients. Higher scores indicate greater fatigue |
| Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Assessed using the Chalder Fatigue Scale (CFQ-11) and/or EORTC QLQ-FA12 for cancer patients. Higher scores indicate greater fatigue |
| Change from Baseline in Fatigue (Chalder Fatigue Scale and/or EORTC QLQ-FA12 for cancer patients) (at 24 weeks after the end of ozone therapy). | At 24 weeks after the end of ozone therapy (approx. week 40). | Assessed using the Chalder Fatigue Scale (CFQ-11) and/or EORTC QLQ-FA12 for cancer patients. Higher scores indicate greater fatigue |
| Change from Baseline in Heart Rate Variability (HRV), (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Non-invasive assessment of the Autonomic Nervous System (vagal tone) by analyzing time intervals between heartbeats (RR intervals). |
| Change from Baseline in Pain Score (Visual Analog Scale), (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Self-reported evaluation of pain severity using a Visual Analog Scale (VAS), scored from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| Change from Baseline in Pain Score (Visual Analog Scale), (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Self-reported evaluation of pain severity using a Visual Analog Scale (VAS), scored from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| Change from Baseline in Pain Score (Visual Analog Scale), (at 24 weeks after the end of ozone therapy). | At 24 weeks after the end of ozone therapy (approx. week 40). | Self-reported evaluation of pain severity using a Visual Analog Scale (VAS), scored from 0 (No pain) to 10 (Pain as bad as you can imagine). |
| 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). | At the end of ozone therapy (approx. week 16). | 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). |
| Change from Baseline in Health-Related Quality of Life by the EQ-5D-5L Questionnaire (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Self-reported evaluation of 5 physical and emotional items scored in five levels, plus a Visual Analog Scale (EQ-VAS) from 0 (worst health) to 100 (best health). |
| Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale, (at 24 weeks after the end of ozone therapy). | At 24 weeks after the end of ozone therapy (approx. week 40). | 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). |
| Change from Baseline in Electrochemical Skin Conductance (Sudoscan), (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Non-invasive evaluation of sudomotor function (small fiber neuropathy assessment). Measured in microsiemens (µS) on hands and feet using SUDOSCAN technology. |
| Change from Baseline in Electrochemical Skin Conductance (Sudoscan), (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Non-invasive evaluation of sudomotor function (small fiber neuropathy assessment). Measured in microsiemens (µS) on hands and feet using SUDOSCAN technology. |
| Change from Baseline in Vibration Perception Thresholds (Multifrequency Vibrometry), (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Assessment of large fiber nerve function using the VibroSense Meter II. Measures perception thresholds at different frequencies (e.g., 4Hz to 500Hz). |
| Change from Baseline in Vibration Perception Thresholds (Multifrequency Vibrometry), (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Assessment of large fiber nerve function using the VibroSense Meter II. Measures perception thresholds at different frequencies (e.g., 4Hz to 500Hz). |
| Change from Baseline in Postural Stability (Equilibrium Platform), (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Functional assessment of balance and Center of Pressure (CoP) displacement using specific force platforms. |
| Change from Baseline in Postural Stability (Equilibrium Platform), (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Functional assessment of balance and Center of Pressure (CoP) displacement using specific force platforms. |
| Change from Baseline in Heart Rate Variability (HRV), (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Non-invasive assessment of the Autonomic Nervous System (vagal tone) by analyzing time intervals between heartbeats (RR intervals). |
| Changes from baseline in Hyperspectral signatures and Infrared images obtained from hands and feet at the end of follow-up, (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Assessment of the percentage of reflectance for each wavelength of the hyperspectral and infrared images obtained with specific devices. |
| Changes from baseline in Hyperspectral signatures and Infrared images obtained from hands and feet at the end of follow-up, (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Assessment of the percentage of reflectance for each wavelength of the hyperspectral and infrared images obtained with specific devices. |
| Changes from baseline in biochemical parameters of oxidative stress and inflammation (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Changes in serum levels of oxidative stress parameters (superoxide dismutase, glutathione, glutathione peroxidase, and free radicals) and proinflammatory cytokines. |
| Changes from baseline in biochemical parameters of oxidative stress and inflammation (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Changes in serum levels of oxidative stress parameters (superoxide dismutase, glutathione, glutathione peroxidase, and free radicals) and proinflammatory cytokines. |
| Change from Baseline in Gut Microbiota Composition (at the end of ozone therapy). | At the end of ozone therapy (approx. week 16). | Analysis of stool samples to evaluate changes in the intestinal microbiome (in patients treated with rectal ozone). |
| Change from Baseline in Gut Microbiota Composition (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | Analysis of stool samples to evaluate changes in the intestinal microbiome (in patients treated with rectal ozone). |
| Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale, (at 12 weeks after the end of ozone therapy). | At 12 weeks after the end of ozone therapy (approx. week 28). | 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). |
Countries
Spain
Contacts
Primary ContactBernardino Clavo, MD, PhD.
Backup ContactFrancisco Rodríguez-Esparragón, BSc, PhyD
Outcome results
None listed