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

Chronic Pain Clinical Trial

— EPOOzo  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05417737
• Other study ID #: DrNegrinUH
• Secondary ID: 2022-203-1
• Status: Recruiting
• Start date: June 15, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Dr. Negrin University Hospital
• Contact: Bernardino Clavo, MD, PhyD
• Phone: (34)928449278
• Email: bernardinoclavo[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults > = 18 years old.

2. 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.

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 have signed and dated the informed consent for the compassionated ozone treatment and the specific informed consent for this study

Exclusion Criteria:

1. Age < 18 years old.

2. Psychiatric illness or social situations that would limit compliance with study requirements.

3. Those who are incapable to fill in the scales used to measure variables.

4. Hemodynamically or clinically unstable patients or uncontrolled severe illness.

5. Uncontrolled cancer disease requiring chemotherapy treatment.

6. Life expectancy < 6 months

7. Contraindication or disability or to attend scheduled treatments.

8. Known allergy to ozone.

9. 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

Related Conditions & MeSH terms

• Chemotherapeutic Toxicity
• Chemotherapy-induced Peripheral Neuropathy
• Chronic Pain
• Delayed Wound Healing
• Pain, Intractable
• Peripheral Nervous System Diseases
• Radiation Toxicity
• Refractory Pain

Intervention

Other:
• Ozone therapy
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.

Locations

Country	Name	City	State
Spain	Dr. Negrín University Hospital	Las Palmas

Sponsors (6)

Lead Sponsor	Collaborator
Bernardino Clavo, MD, PhD	Cabildo de Gran Canaria, Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC), Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Red de Investigación en Servicios de Salud en Enfermedades Crónicas, Servicio Canario de Salud

Country where clinical trial is conducted

Spain, 

References & Publications (11)

Clavo 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): — View Citation

Clavo 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. — View Citation

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. — View Citation

Clavo 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 Treat — View Citation

Clavo 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 Explo — View Citation

Clavo 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. — View Citation

Clavo 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. — View Citation

Clavo 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 — View Citation

Clavo 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 Ba — View Citation

Clavo 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 Ma — View Citation

Clavo 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from Baseline in the main symptoms (at the end of ozone therapy)	Self -reported percentage of symptom improvement from Baseline	16 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from Baseline in the main symptoms.	Self -reported percentage of symptom improvement from Baseline	28 weeks
Secondary	Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).	Serum levels of biochemical parameters of oxidative stress	28 weeks
Secondary	Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).	Serum levels of pro-inflammatory cytokines	28 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Changes from Baseline in the main symptoms.	Self -reported percentage of symptom improvement from Baseline	40 weeks
Secondary	Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).	Serum levels of biochemical parameters of oxidative stress	40 weeks
Secondary	Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).	Serum levels of pro-inflammatory cytokines	40 weeks