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RecruitingNCT06706544OzoParQTUpdated Sep 18, 2026

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

A Phase 2/3 interventional study of Ozone therapy and Oxygen (placebo) in Chemotherapy Induced Peripheral Neuropathy (CIPN), Paresthesia and Numbness, sponsored by Bernardino Clavo, MD, PhD. Recruiting at 1 site in Spain. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-18.

Sponsored by Bernardino Clavo, MD, PhD · Phase 2/3, Interventional, and Treatment

From the registry’s dates

  • Started Feb 2025; still recruiting 1 year 9 months later.
Phase
Phase 2/3
Study type
Interventional
Enrollment
42
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.
Read the 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).
02

Conditions studied

  • Chemotherapy Induced Peripheral Neuropathy (CIPN)
  • Paresthesia
  • Numbness
  • Tingling

Keywords

  • Chemotherapy induced peripheral neuropathy
  • paresthesia
  • numbness and tingling
  • side effect of cancer treatment
  • toxicity of chemotherapy
  • ozone therapy
  • quality of life
  • anxiety
  • depression
  • hyperspectral imaging
  • oxidative stress
03

In context

Paresthesia

66 studies on the registry are indexed under Paresthesia; 14 are open to participants now.

This study's planned enrollment of 42 is below the median of 48 across 52 interventional studies indexed under Paresthesia.

Browse Paresthesia studies →

Lead sponsor

Bernardino Clavo, MD, PhD is the lead sponsor of 10 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 () 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. > = 6 months.
  • 7. Before enrollment, women of should obtain a negative result in the serum or urine pregnancy test at the screening visit and accept the use of appropriate 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

Exclusion criteria

Exclusion Criteria:

  • 1. Age \< 18 years.
  • 2. A woman who is lactating, pregnant, suspected of being pregnant, or a woman of who does not use adequate 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. (for any reason) \< 6 months.
  • 10. Known allergy to ozone, known glucose 6 phosphate dehydrogenase (G6PD) deficiency, or hemochromatosis.
  • 11. or impossibility for rectal ozone treatment or to attend regularly to the treatment.
  • 12. Not meeting each and every one of the inclusion criteria
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Outcomes assessor)
Enrollment
42 participants (estimated)

Study arms

  • 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

  • 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)

Interventions

  • DrugOzone 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.

    Also known as: Ozone treatment, O3, O3/O2 gas mixture

  • DrugOxygen (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.

    Also known as: O2

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 28 weeks

  2. 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).

    Time frame: 28 weeks

Secondary outcomes

  1. 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).

    Time frame: 28 weeks

  2. 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).

    Time frame: 16

  3. 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).

    Time frame: 16 weeks

  4. 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).

    Time frame: 16 weeks.

  5. 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.

    Time frame: 16 weeks.

  6. 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).

    Time frame: 16 weeks.

  7. 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).

    Time frame: 16 weeks.

  8. 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).

    Time frame: 16 weeks

  9. 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

    Time frame: 16 weeks.

  10. Changes from baseline in biochemical parameters of inflammation at the end of ozone treatment.

    Changes in serum levels of pro-inflammatory cytokines.

    Time frame: 16 weeks

  11. 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.

    Time frame: 16 weeks

  12. 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).

    Time frame: 28 weeks.

  13. 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).

    Time frame: 28 weeks

  14. 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: Time frame: 28 weeks

  15. 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).

    Time frame: 28 weeks.

  16. 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).

    Time frame: 28 weeks.

  17. 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.

    Time frame: 28 weeks.

  18. Changes from baseline in biochemical parameters of inflammation at the end of follow-up.

    Changes in serum levels of pro-inflammatory cytokines.

    Time frame: 28 weeks.

  19. 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.

    Time frame: 28 weeks.

  20. 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).

    Time frame: 28 weeks.

07

Study locations

1 of 1 sites recruiting
  • Dr. Negrín University Hospital
    Las Palmas, Las Palmas 35019, Spain
    Recruiting
    • Bernardino Clavo, MD, PhD · Contactbernardinoclavo@gmail.com · 34928449278
    • Francisco Rodríguez-Esparragón, BSc, PhD · Contactafrodesp@gmail.com · 34928449288
    • Bernardino Clavo, MD, PhD · Principal investigator
    • Francisco Rodríguez-Esparragón, BSc, PhD · Principal investigator
08

References and documents

Publications

  • 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. PubMed 34360655 ↗
  • 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. PubMed 34943049 ↗
  • 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. PubMed 36982352 ↗
  • 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. PubMed 23549581 ↗
  • 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. PubMed 23046293 ↗
  • 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. PubMed 35283802 ↗
  • 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. PubMed 31426459 ↗
  • 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. PubMed 22105041 ↗
  • 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. PubMed 31779159 ↗
  • 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. PubMed 33738491 ↗
  • 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. PubMed 32379556 ↗
  • 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. PubMed 36111149 ↗
  • 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 33802143 ↗
  • 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. PubMed 23102757 ↗
  • 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. PubMed 36674232 ↗
  • 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. PubMed 37599784 ↗
  • 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. PubMed 21575276 ↗
  • 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. PubMed 25699252 ↗
  • 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. PubMed 19260079 ↗
  • Clavo B, Canovas-Molina A, Cazorla-Rivero S, Martinez-Sanchez G, Galvan S, Benitez G, Federico M, Fabelo H, Gonzalez-Martin JM, Garcia-Bello MA, Lago-Moreno E, Antonilli C, Ramchandani A, Diaz-Garrido JA, Navarro M, Martin-Alfaro R, Hernandez-Lopez H, Callico GM, Rodriguez-Esparragon F. Effectiveness and cost-effectiveness of ozone treatment in patients with paraesthesia (numbness, tingling) secondary to chemotherapy-induced peripheral neuropathy: randomized, triple-blind clinical trial (OzoParQT). BMC Cancer. 2026 Jan 22;26(1):260. doi: 10.1186/s12885-025-15399-9. PubMed 41572235 ↗

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: Data will be available after publication, ending 36 months following article publication.

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.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Feb 2025 (actual). Primary completion is estimated for Dec 2029, 58 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 22, 2024
First posted
Nov 26, 2024
StartActual
Feb 7, 2025
Primary completionEst.
Dec 31, 2029
CompletionEst.
Mar 31, 2030
Last update
Sep 18, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 18, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06706544
Lead sponsor
Bernardino Clavo, MD, PhD
Collaborators
Council of Gran Canaria, Centers for International Business Education and Research, Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Complejo Hospitalario Universitario Insular Materno Infantil, Servicio Canario de Salud, University of Las Palmas de Gran Canaria, Instituto de Salud Carlos III
Responsible party
Bernardino Clavo, MD, PhD (Bernardino Clavo, MD, PhD, Dr. Negrin University Hospital, Hospital Universitario de Gran Canaria Doctor Negrín) — Sponsor-investigator
First posted
Nov 26, 2024
Start date
Feb 7, 2025
Primary completion
Dec 31, 2029 (estimated)
Completion
Mar 31, 2030 (estimated)
Last update
Sep 18, 2026

Study contacts

Bernardino Clavo, MD, PhD
Contact
bernardinoclavo@gmail.com
34928449278
Francisco Rodríguez-Esparragón, BSc, PhD
Contact
afrodesp@gmail.com
34928449288
Bernardino Clavo, MD, PhD
study chair · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain
Francisco Rodríguez-Esparragón, BSc, PhD
study director · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain
Himar Fabelo, BSc, PhD
principal investigator · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain
Gustavo M Callicó, Prof, PhD
principal investigator · University of Las Palmas de Gran Canaria
Francisco Rodríguez-Esparragón, BSc, PhD
principal investigator · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain
Bernardino Clavo, MD, PhD
principal investigator · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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