Radiation ToxicityEPOOzoNCT05417737
Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2022 and 2025
An observational study of Radiation Toxicity and Chemotherapeutic Toxicity, run by Bernardino Clavo, MD, PhD at 1 site in Spain.
Trial 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 HUGCDN Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between June-2022 and December-2025 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Radiation Toxicity, Chemotherapeutic Toxicity, Chemotherapy-induced Peripheral Neuropathy
- What is being tested?
- Ozone therapy
- How many people
- 105 participants
- Where
- 1 siteSpain
- Study dates
- 15 Jun 2022to 30 Oct 2026
- How long will I take part?
- 28 Weeks
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients submitted to the Chronic Pain Unit of the Hospital Universitario de Gran Canaria Dr. Negrín for symptomatic/palliative treatment with ozone therapy because standard treatment does not exist, it has been unsuccessful, or it is associated with high risk or high morbidity.
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective and Observational Study of Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2022 and 2025. (EPOOzo)
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
Read the detailed description
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.
- Conditions
- Radiation Toxicity, Chemotherapeutic Toxicity, Chemotherapy-induced Peripheral Neuropathy, Delayed Wound Healing, Chronic Pain, Refractory Pain
- Being tested
- Ozone therapy
- Keywords
- 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
- Medical subject headings
- Radiation Injuries, Chronic Pain, Pain, Intractable, Anxiety Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ozone therapyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Ozone group | 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. Receives: Other: Ozone therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 16 weeks
Secondary outcomes (23)
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).
Measured: 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")
Measured: 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).
Measured: 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.
Measured: 16 weeks
Changes from Baseline in the main symptoms (at the end of ozone therapy)
Self -reported percentage of symptom improvement from Baseline
Measured: 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
Measured: 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
Measured: 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)
Measured: 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).
Measured: 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")
Measured: 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).
Measured: 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.
Measured: 28 weeks
Changes from Baseline in the main symptoms.
Self -reported percentage of symptom improvement from Baseline
Measured: 28 weeks
Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).
Serum levels of biochemical parameters of oxidative stress
Measured: 28 weeks
Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).
Serum levels of pro-inflammatory cytokines
Measured: 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)
Measured: 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).
Measured: 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")
Measured: 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).
Measured: 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.
Measured: 40 weeks
Changes from Baseline in the main symptoms.
Self -reported percentage of symptom improvement from Baseline
Measured: 40 weeks
Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).
Serum levels of biochemical parameters of oxidative stress
Measured: 40 weeks
Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).
Serum levels of pro-inflammatory cytokines
Measured: 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2022
- Study start15 Jun 2022
- Primary completion30 Apr 2026
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Radiation ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 105 participants (estimated)
- Target duration
- 28 Weeks
Sponsor and investigators
- Lead sponsor
- Bernardino Clavo, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Servicio Canario de Salud, Council of Gran Canaria, Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna
- Responsible party
- Sponsor-investigator, Bernardino Clavo, MD, PhD, Hospital Universitario de Gran Canaria Doctor Negrín
- Investigators
- Bernardino Clavo, MD, PhyD, Study chair, Dr. Negrín University Hospital, Las Palmas, SpainPedro G Serrano-Aguilar, MD, PhyD, Study director, Servicio de Evaluación. Servicio Canario de Salud. SpainBernardino Clavo, MD, PhyD, Principal investigator, Dr. Negrín University Hospital, Las Palmas, SpainMiguel A Caramés-Álvarez, MD, Principal investigator, Dr. Negrín University Hospital, Las Palmas, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05417737
- Sponsor's protocol ID
- DrNegrinUH
- Other IDs
- 2022-203-1
- Acronym
- EPOOzo
- Status last verified
- Sep 2026
- First submitted
- 3 Jun 2022
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Clavo B, Martinez-Sanchez G, Rodriguez-Esparragon F, Rodriguez-Abreu D, Galvan S, Aguiar-Bujanda D, Diaz-Garrido JA, Canas S, Torres-Mata LB, Fabelo H, Tellez T, Santana-Rodriguez N, Fernandez-Perez L, Marrero-Callico G. Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial. Int J Mol Sci. 2021 Mar 10;22(6):2802. doi: 10.3390/ijms22062802.
PubMed 33802143Clavo B, Rodriguez-Esparragon F, Rodriguez-Abreu D, Martinez-Sanchez G, Llontop P, Aguiar-Bujanda D, Fernandez-Perez L, Santana-Rodriguez N. Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects. Antioxidants (Basel). 2019 Nov 26;8(12):588. doi: 10.3390/antiox8120588.
PubMed 31779159Clavo 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.
PubMed 33738491Clavo 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.
PubMed 32379556Clavo B, Santana-Rodriguez N, Llontop P, Gutierrez D, Suarez G, Lopez L, Rovira G, Martinez-Sanchez G, Gonzalez E, Jorge IJ, Perera C, Blanco J, Rodriguez-Esparragon F. Ozone Therapy as Adjuvant for Cancer Treatment: Is Further Research Warranted? Evid Based Complement Alternat Med. 2018 Sep 9;2018:7931849. doi: 10.1155/2018/7931849. eCollection 2018.
PubMed 30271455Clavo 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.
PubMed 26357522Clavo B, Santana-Rodriguez N, Gutierrez D, Lopez JC, Suarez G, Lopez L, Robaina F, Bocci V. Long-term improvement in refractory headache following ozone therapy. J Altern Complement Med. 2013 May;19(5):453-8. doi: 10.1089/acm.2012.0273. Epub 2012 Dec 7.
PubMed 23215625Clavo 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.
PubMed 23102757Clavo B, Santana-Rodriguez N, Lopez-Silva SM, Dominguez E, Mori M, Gutierrez D, Hernandez MA, Robaina F. Persistent PORT-A-CATH(R)-related fistula and fibrosis in a breast cancer patient successfully treated with local ozone application. J Pain Symptom Manage. 2012 Feb;43(2):e3-6. doi: 10.1016/j.jpainsymman.2011.09.002. No abstract available.
PubMed 22248793Clavo B, Suarez G, Aguilar Y, Gutierrez D, Ponce P, Cubero A, Robaina F, Carreras JL. Brain ischemia and hypometabolism treated by ozone therapy. Forsch Komplementmed. 2011;18(5):283-7. doi: 10.1159/000333795. Epub 2011 Oct 13.
PubMed 22105041Clavo B, Gutierrez D, Martin D, Suarez G, Hernandez MA, Robaina F. Intravesical ozone therapy for progressive radiation-induced hematuria. J Altern Complement Med. 2005 Jun;11(3):539-41. doi: 10.1089/acm.2005.11.539.
PubMed 15992242