Ozone Treatment in Paresthesia (numbness, Tingling) Secondary to Chemotherapy-induced Peripheral Neuropathy (OzoParQT)

Effectiveness and Cost-effectiveness of Ozone Treatment in Patients with Paresthesia (numbness, Tingling) Secondary to Chemotherapy-induced Peripheral Neuropathy. Randomized, Triple-blind Clinical Trial (OzoParQT)

The goal of this phase II/III randomized clinical trial is to evaluate the effect of adding rectal ozone therapy to the usual management of patients with paresthesia (numbness and/or tingling) due to chemotherapy-induced peripheral neuropathy (CIPN). Ozone treatment consists of the rectal insufflation of 180 - 300 milliliters of an ozone/oxygen gas mixture.

The main questions to answer are:

1. Can ozone therapy improve patients' self-perceived level of numbness and tingling?
2. Can ozone therapy improve patients' self-perceived health-related quality of life (HRQoL)?

In 42 patients with chronic numbness and tingling secondary to chemotherapy, the researchers will compare:

• the addition of rectal ozone insufflations
• versus the addition of rectal oxygen insufflations (placebo). Participants will receive 40 rectal gas (ozone versus oxygen) insufflations in 16 weeks and will continue other symptomatic or cancer treatments prescribed by their oncologists.

Before treatment, after treatment, and 12 weeks after treatment, they will be evaluated:

• Several questionnaires about neuropathy, quality of life, and anxiety and depression.
• Biochemical parameters of oxidative stress and inflammation
• Hyperspectral images of hands and feet
• Toxicity of procedure.

Study Overview

• Status: Recruiting
• Conditions: Paresthesia; Chemotherapy Induced Peripheral Neuropathy (CIPN); Numbness; Tingling
• Intervention / Treatment: Drug: Ozone therapy; Drug: Oxygen (placebo)

Detailed Description

Rationale Chemotherapy-induced peripheral neuropathy (CIPN) can lead to a decrease and/or interruption of chemotherapy treatment, limiting its efficacy and decreasing patients' quality of life. Therapeutic measures for CIPN are very limited in number and efficacy. Our previous experience has suggested the potential clinical usefulness of adjuvant treatment with ozone in patients with CIPN. The hypothesis of the trial is that ozone treatment will improve numbness and tingling symptoms in patients with CIPN.

Primary objectives:

To evaluate the effect of adding ozone to the usual management of patients with paresthesia (numbness and/or tingling) due to chemotherapy-induced peripheral neuropathy (CIPN), Grade 2 (moderate symptoms and/or limitation in instrumental activities of daily living) or higher, on:

1. patients' self-perceived level of paresthesia
2. patients' self-perceived health-related quality of life (HRQoL).

Secondary objectives:

To evaluate (in patients with numbness and/or tingling secondary to CIPN) the effect of adding ozone to the usual management on:

1. the additional direct costs incurred in the application of ozone and evaluate the cost-effectiveness of the administration of ozone in these patients in comparison with the usual exclusive treatment.
2. the evolution of the sensory neuropathy
3. the evolution of the level of anxiety and depression,
4. the evolution of biochemical parameters related to oxidative stress and chronic inflammation.
5. the evolution of hyperspectral signatures obtained from hands and feet.
6. to evaluate the toxicity of rectal ozone treatment in these patients.

Main trial endpoints.

1. Percentage of change from baseline in "numbness and tingling" self-perceived by patients at the end of follow-up (week 28 after the commencement of ozone treatment)
2. Change from baseline in "quality of life" (using the EQ-5D-5L questionnaire) self-perceived by patients at the end of follow-up (week 28 after the commencement of ozone treatment)

Secondary trial endpoints.

To evaluate the percentage of change from baseline in all the secondary objectives:

• at the end of ozone treatment (weeks 16)
• and at the end of follow-up (week 28)

Trial design. Phase II-III randomized triple-blind clinical trial. The duration of each patient in the study will be 28 weeks: 16 weeks of treatment and 12 weeks of follow-up. The planned total duration of the project is 60 months.

Trial population. 42 adult patients (>= 18 years old), with any tumor, with paresthesias (numbness and/or tingling) due to CIPN, grade of toxicity >= 2 (according to the Common Toxicity Criteria for Adverse Events (CTCAE) from the National Cancer Institute of EEUU, v.5.0), for >= 3 months.

Intervention.

All patients will receive the usual management and treatment for their symptoms + "40 sessions of rectal insufflation of O3/O2 gas mixture" in 16 weeks (3 or 2 sessions per week):

• Ozone group, O3/O2 concentration increasing from 10 to 30 µg/mL (µg of O3 by mL of O2).
• Control-placebo group, O3/O2 concentration = 0 µg/mL (this is: only O2).

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Bernardino Clavo, MD, PhD; Phone Number: 34928449278; Email: bernardinoclavo@gmail.com
• Study Contact Backup: Name: Francisco Rodríguez-Esparragón, BSc, PhD; Phone Number: 34928449288; Email: afrodesp@gmail.com

Study Locations

• Spain
  • Las Palmas, Spain, 35019
    • Recruiting
    • Dr. Negrín University Hospital
    • Contact: Bernardino Clavo, MD, PhD; Phone Number: 34928449278; Email: bernardinoclavo@gmail.com
    • Contact: Francisco Rodríguez-Esparragón, BSc, PhD; Phone Number: 34928449288; Email: afrodesp@gmail.com
    • Contact: Bernardino Clavo, MD, PhD
    • Contact: Francisco Rodríguez-Esparragón, BSc, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Adults > = 18 years old.
• 2. Previous treatment with any chemotherapy because of any tumor.
• 3. Clinical diagnosis of paresthesia (numbness, tingling) secondary to CIPN, with toxicity Grade > = 2 (according to the Common Toxicity Criteria for Adverse Events (CTCAE) from the National Cancer Institute of EEUU, v.5.0) for > = 3 months.
• 4. Without neurotoxic chemotherapy > = 3 months.
• 5. Cancer disease is stable or in remission.
• 6. Life expectancy > = 6 months.
• 7. Before enrollment, women of childbearing potential should obtain a negative result in the serum or urine pregnancy test at the screening visit and accept the use of appropriate contraceptive methods at least from 14 days before the first ozone therapy session up to 14 days after the last one.
• 8. To sign and date the study-specific informed consent

Exclusion Criteria:

• 1. Age < 18 years.
• 2. A woman who is lactating, pregnant, suspected of being pregnant, or a woman of childbearing potential who does not use adequate contraceptive methods.
• 3. Suspected symptoms are due to diabetic or compressive neuropathy.
• 4. Severe psychiatric disorders.
• 5. Inability to complete the quality of life questionnaires.
• 6. Elevation above 5 times the maximum limit of normal creatinine.
• 7. Patient who is hemodynamic or clinically unstable or who requires urgent or short-term interventional measures.
• 8. Neoplasia in progression requiring recent initiation of systemic treatment or maintenance with neurotoxic chemotherapy.
• 9. Life expectancy (for any reason) < 6 months.
• 10. Known allergy to ozone, known glucose 6 phosphate dehydrogenase (G6PD) deficiency, or hemochromatosis.
• 11. Contraindications or impossibility for rectal ozone treatment or to attend regularly to the treatment.
• 12. Not meeting each and every one of the inclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ozone Group; Drug: Ozone (O3/O2). Treatment: Usual treatment + Ozone therapy by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.	Drug: Ozone therapy; Usual treatment (by their oncologist or hematologist) + Ozone therapy by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.; Other Names: O3; Ozone treatment; O3/O2 gas mixture
Placebo Comparator: Oxygen Group (Placebo); Drug: Oxygen (O2). Treatment: Usual treatment + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.	Drug: Oxygen (placebo); Usual treatment (by their oncologist or hematologist) + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.; Other Names: O2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in "numbness and tingling" self-perceived by patients at the end of follow-up (week 28 after the commencement of ozone treatment)	Self-reported evaluation of the percentage of "numbness and/or tingling" regarding the basal level. From 100% (basal level, 0% improvement) to 0% (no numbness and tingling, 100% improvement).	28 weeks
Change from Baseline in quality of life by the EQ-...	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 an extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analog scale (0 = worst health patient can imagine, 100 = best health patient can imagine).	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Direct hospital costs	The direct expenses incurred by the hospital in providing services (medication, tests, medical visits…) during the 28 weeks for the study (in euros).	28 weeks
Change from baseline in "numbness and tingling" self-perceived by patients at the end of ozone treatment.	Self-reported evaluation of the percentage of "numbness and/or tingling" regarding the basal level. From 100% (basal level, 0% improvement) to 0% (no numbness and tingling, 100% improvement).	16
Changes from baseline in the Grade of toxicity of parestesias (numbness, tingling) according to the CTCAE v.5.0. scale at the end of ozone treatment.	Changes from baseline in the Grade of toxicity of paresthesias (numbness, tingling) according to the CTCAE v.5.0. scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities in daily life).	16 weeks
Changes from baseline in the Grade of toxicity of sensory neuropathy according to the CTCAE v.5.0. scale at the end of ozone treatment.	Changes from baseline in the Grade of toxicity of paresthesias (numbness, tingling) according to the CTCAE v.5.0. scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 4 (life-threatening consequences, urgent intervention indicated).	16 weeks.
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment.	Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment (from the European Organization for Research & Treatment in Cancer (EORTC)). It is evaluated through 20 items that are grouped into 3 dimensions: sensitive, motor and autonomic. Range: each item is scored from 1 (nothing) to 4 (a lot). The total score for each dimension is transformed into a score from 0 to 1000, being 0 the best state and 100 the worst.	16 weeks.
Change from baseline in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients at the end of ozone treatment (week 16 after the commencement of ozone treatment).	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 an extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analog scale (0 = worst health patient can imagine, 100 = best health patient can imagine).	16 weeks.
Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire at the end of ozone treatment.	Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire (from the European Organization for Research & Treatment in Cancer (EORTC)). Self-reported evaluation of 30 items that measure several scales and symptoms. Range (after standardization): from 0 (worst for overall health and function, best for symptoms) to 100 (best for overall health and functions, worst for symptoms).	16 weeks.
Changes from baseline in levels of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS), at the end of ozone treatment.	Changes from baseline in levels of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS). HADS is a self-administered questionnaire that assesses 14 items/symptoms of anxiety (7) and depression (7) experienced by patients. Each item is scored from 0 (better, no alteration) to 3 (worse level of alteration). For each symptom (anxiety or depression), the overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression).	16 weeks
Changes from baseline in biochemical parameters of oxidative stress at the end of ozone treatment.	Changes in serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals	16 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of ozone treatment.	Changes in serum levels of pro-inflammatory cytokines.	16 weeks
Changes from baseline in Hyperspectral signatures and infrared images obtained from hands and feet at then of ozone treatment.	Assessment of the percentage of reflectance for each wavelength of the hyperspectral and infrared images obtained with specific devices.	16 weeks
Changes from baseline in the Grade of toxicity of paresthesias (numbness, tingling) according to the CTCAE v.5.0. scale at the end of follow-up.	Changes from baseline in the Grade of toxicity of paresthesias (numbness, tingling) according to the CTCAE v.5.0. scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities in daily life).	28 weeks.
Changes from baseline in the Grade of toxicity of sensory neuropathy according to the CTCAE v.5.0. scale at the end of follow-up.	Changes from baseline in the Grade of toxicity of paresthesias (numbness, tingling) according to the CTCAE v.5.0. scale (from the National Cancer Institute of EEUU). Range from: Grade = (asymptomatic or mild symptoms) to Grade 4 (life-threatening consequences, urgent intervention indicated).	28 weeks
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of follow-up.	Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment (from the European Organization for Research & Treatment in Cancer (EORTC)). It is evaluated through 20 items that are grouped into 3 dimensions: sensitive, motor, and autonomic. Range: each item is scored from 1 (nothing) to 4 (a lot). The total score for each dimension is transformed into a score from 0 to 1000, being 0 the best state and 100 the worst.	Time frame: 28 weeks
Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire at the end of follow-up.	Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire (from the European Organization for Research & Treatment in Cancer (EORTC)). Self-reported evaluation of 30 items that measure several scales and symptoms. Range (after standardization): from 0 (worst for overall health and function, best for symptoms) to 100 (best for overall health and functions, worst for symptoms).	28 weeks.
Changes from baseline in levels of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS) at the end of follow-up.	Changes from baseline in levels of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS). HADS is a self-administered questionnaire that assesses 14 items/symptoms of anxiety (7) and depression (7) experienced by patients. Each item is scored from 0 (better, no alteration) to 3 (worse level of alteration). For each symptom (anxiety or depression), the overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression).	28 weeks.
Changes from baseline in biochemical parameters of oxidative stress at the end of follow-up.	Changes in serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals.	28 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of follow-up.	Changes in serum levels of pro-inflammatory cytokines.	28 weeks.
Changes from baseline in Hyperspectral signatures and infrared images obtained from hands and feet at the end of follow-up.	Assessment of the percentage of reflectance for each wavelength of the hyperspectral and infrared images obtained with specific devices.	28 weeks.
Toxicity of rectal ozone treatment at the end of follow-up.	Grade of toxicity secondary to the rectal insufflation of the rectal ozone treatment according to the CTCAE v.5.0. scale (from the National Cancer Institute of EEUU).	28 weeks.

Collaborators and Investigators

• Sponsor: Bernardino Clavo, MD, PhD
• Collaborators: Instituto de Salud Carlos III; CIBER (Infectious diseases); Complejo Hospitalario Universitario Insular Materno Infantil; Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias (FIISC); Servicio de Evaluacion del Servicio Canario de Salud.; Institute for Applied Microelectronics, University of Las Palmas de Gran Canaria, Spain; Council of Gran Canaria
• Investigators: Study Chair: Bernardino Clavo, MD, PhD, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain; Study Director: Francisco Rodríguez-Esparragón, BSc, PhD, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain; Principal Investigator: Himar Fabelo, BSc, PhD, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain; Principal Investigator: Gustavo M Callicó, Prof, PhD, Institute for Applied Microelectronics, University of Las Palmas de Gran Canaria, Spain; Principal Investigator: Francisco Rodríguez-Esparragón, BSc, PhD, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain; Principal Investigator: Bernardino Clavo, MD, PhD, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

Publications and helpful links

General 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.
• Clavo B, Rodriguez-Abreu D, Galvan S, Federico M, Martinez-Sanchez G, Ramallo-Farina Y, Antonelli C, Benitez G, Rey-Baltar D, Jorge IJ, Rodriguez-Esparragon F, Serrano-Aguilar P. Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report. Front Physiol. 2022 Aug 30;13:935269. doi: 10.3389/fphys.2022.935269. eCollection 2022.
• Bocci V, Valacchi G. Nrf2 activation as target to implement therapeutic treatments. Front Chem. 2015 Feb 2;3:4. doi: 10.3389/fchem.2015.00004. eCollection 2015.
• Bocci VA, Zanardi I, Travagli V. Ozone acting on human blood yields a hormetic dose-response relationship. J Transl Med. 2011 May 17;9:66. doi: 10.1186/1479-5876-9-66.
• Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev. 2009 Jul;29(4):646-82. doi: 10.1002/med.20150.
• Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL; Alliance for Clinical Trials in Oncology. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.
• 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.
• Viebahn-Haensler R, Leon Fernandez OS. Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases. Int J Mol Sci. 2021 Jul 23;22(15):7890. doi: 10.3390/ijms22157890.
• Tricarico G, Travagli V. The Relationship between Ozone and Human Blood in the Course of a Well-Controlled, Mild, and Transitory Oxidative Eustress. Antioxidants (Basel). 2021 Dec 4;10(12):1946. doi: 10.3390/antiox10121946.
• Szklener K, Rudzinska A, Juchaniuk P, Kabala Z, Mandziuk S. Ozone in Chemotherapy-Induced Peripheral Neuropathy-Current State of Art, Possibilities, and Perspectives. Int J Mol Sci. 2023 Mar 9;24(6):5279. doi: 10.3390/ijms24065279.
• Hidalgo-Tallon J, Menendez-Cepero S, Vilchez JS, Rodriguez-Lopez CM, Calandre EP. Ozone therapy as add-on treatment in fibromyalgia management by rectal insufflation: an open-label pilot study. J Altern Complement Med. 2013 Mar;19(3):238-42. doi: 10.1089/acm.2011.0739. Epub 2012 Oct 9.
• Hidalgo-Tallon FJ, Torres-Morera LM, Baeza-Noci J, Carrillo-Izquierdo MD, Pinto-Bonilla R. Updated Review on Ozone Therapy in Pain Medicine. Front Physiol. 2022 Feb 23;13:840623. doi: 10.3389/fphys.2022.840623. eCollection 2022.
• Galie M, Covi V, Tabaracci G, Malatesta M. The Role of Nrf2 in the Antioxidant Cellular Response to Medical Ozone Exposure. Int J Mol Sci. 2019 Aug 17;20(16):4009. doi: 10.3390/ijms20164009.
• 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.
• 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.
• 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.
• 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.
• Clavo B, Canovas-Molina A, Ramallo-Farina Y, Federico M, Rodriguez-Abreu D, Galvan S, Ribeiro I, Marques da Silva SC, Navarro M, Gonzalez-Beltran D, Diaz-Garrido JA, Cazorla-Rivero S, Rodriguez-Esparragon F, Serrano-Aguilar P. Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors. Int J Environ Res Public Health. 2023 Jan 13;20(2):1479. doi: 10.3390/ijerph20021479.
• Clavo B, Canovas-Molina A, Diaz-Garrido JA, Canas S, Ramallo-Farina Y, Laffite H, Federico M, Rodriguez-Abreu D, Galvan S, Garcia-Lourve C, Gonzalez-Beltran D, Carames MA, Hernandez-Fleta JL, Serrano-Aguilar P, Rodriguez-Esparragon F. Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study. Front Psychol. 2023 Aug 4;14:1176204. doi: 10.3389/fpsyg.2023.1176204. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: November 22, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: quality of life; depression; anxiety; oxidative stress; hyperspectral imaging; paresthesia; ozone therapy; Chemotherapy induced peripheral neuropathy; numbness and tingling; side effect of cancer treatment; toxicity of chemotherapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Sensation Disorders; Somatosensory Disorders; Peripheral Nervous System Diseases; Paresthesia; Hypesthesia
• Other Study ID Numbers: OzoParQT; PI23/01324 (Other Grant/Funding Number: Instituto de Salud Carlos III); 2024-517196-20-00 (Ctis); 2023-210-1 (Registry Identifier: CEIm Las Palmas); CIGC'23/24 (Other Grant/Funding Number: Cabildo de Gran Canaria)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

It will be available (after request):

• Individual participant data (IPD) that underlie the results reported in further articles, after deidentification
• Data will be available after publication, ending 36 months following article publication.
• They will be available for investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
• Study protocol

Proposals should be directed to: bernardinoclavo@gmail.com To gain access, data requestors will need to sign a data access agreement.

• IPD Sharing Time Frame: Data will be available after publication, ending 36 months following article publication.

IPD Sharing Access Criteria

Data will be available for investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.

- Study protocol

Proposals should be directed to: bernardinoclavo@gmail.com To gain access, data requestors will need to sign a data access agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No