Clinical trial NCT05417737: Patients Referred to the Chronic Pain Unit for Palliative Treatment With Ozone Therapy Between 2022 and 2025
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)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Radiation Toxicity
Chemotherapeutic Toxicity
Chemotherapy-induced Peripheral Neuropathy
Delayed Wound Healing
Chronic Pain
Refractory Pain
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
Lead sponsor: Dr. Negrin University Hospital
Sponsor class: OTHER
Collaborators: name: Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias
name: Servicio Canario de Salud
name: Council of Gran Canaria
name: Red de Investigación en Servicios de Salud en Enfermedades Crónicas
name: Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna
First posted: 2022-06-14
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

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 HUGCDN Chronic Pain Unit for adjuvant palliative treatment with ozone therapy between June-2022 and December-2025

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: 16 weeks
Secondary outcomes:
measure: Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in pain score according to the visual analog scale (VAS) (at the end of ozone therapy)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: Changes from Baseline in the main symptoms (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy) (at the end of ozone therapy).
timeFrame: 16 weeks
measure: Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy) (at the end of of ozone therapy).
timeFrame: 16 weeks
measure: Change from Baseline in the health-related quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire.
timeFrame: 28 weeks
measure: Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale.
timeFrame: 28 weeks
measure: Change from Baseline in pain score according to the visual analog scale (VAS).
timeFrame: 28 weeks
measure: Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale.
timeFrame: 28 weeks
measure: Changes from Baseline in requirements of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management.
timeFrame: 28 weeks
measure: Changes from Baseline in the main symptoms.
timeFrame: 28 weeks
measure: Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).
timeFrame: 28 weeks
measure: Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).
timeFrame: 28 weeks
measure: Change from Baseline in the health-related quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire.
timeFrame: 40 weeks
measure: Change from Baseline in Levels of anxiety and depression according to the hospital anxiety/depression scale.
timeFrame: 40 weeks
measure: Change from Baseline in pain score according to the visual analog scale (VAS).
timeFrame: 40 weeks
measure: Change from Baseline in the grade of toxicity secondary to cancer-treatment (if applicable) according to the CTCAE v5.0 scale.
timeFrame: 40 weeks
measure: Changes from Baseline in requirements of invasive procedures (surgery, blood transfusions, and therapeutic endoscopic procedures) required for symptom management.
timeFrame: 40 weeks
measure: Changes from Baseline in the main symptoms.
timeFrame: 40 weeks
measure: Changes from Baseline in biochemical parameters of oxidative stress (if systemic ozone therapy).
timeFrame: 40 weeks
measure: Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy).
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Las Palmas
country: Spain
facility: Dr. Negrín University Hospital
Study officials:
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Bernardino Clavo, MD, PhyD
role: STUDY_CHAIR
affiliation: Servicio de Evaluación. Servicio Canario de Salud. Spain
name: Pedro G Serrano-Aguilar, MD, PhyD
role: STUDY_DIRECTOR
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Bernardino Clavo, MD, PhyD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Miguel A Caramés-Álvarez, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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 Treatment. Pain Med. 2021 Sep 8;22(9):2138-2141. doi: 10.1093/pm/pnaa459. No abstract available.
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 Exploration. J Palliat Med. 2021 Jan;24(1):97-102. doi: 10.1089/jpm.2019.0597. Epub 2020 May 5.
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 Based Complement Alternat Med. 2018 Sep 9;2018:7931849. doi: 10.1155/2018/7931849. eCollection 2018.
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 Patients. Evid Based Complement Alternat Med. 2015;2015:480369. doi: 10.1155/2015/480369. Epub 2015 Aug 18.
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.
citation: 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):106-12. doi: 10.1016/j.jpainsymman.2012.06.017. Epub 2012 Oct 26.
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 Manage. 2012 Feb;43(2):e3-6. doi: 10.1016/j.jpainsymman.2011.09.002. No abstract available.
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.
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.