Chemotherapy Induced Peripheral Neuropathy (CIPN)Phase 2/3OzoParQTNCT06706544

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

A Phase 2/3 study testing Ozone therapy in people with Chemotherapy Induced Peripheral Neuropathy (CIPN) and Paresthesia, run by Bernardino Clavo, MD, PhD at 1 site in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Chemotherapy Induced Peripheral Neuropathy (CIPN), Paresthesia, Numbness
What is being tested?: Ozone therapy
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 42 participants
Where: 1 siteSpain
Study dates: 7 Feb 2025to 31 Mar 2030
Phase: Phase 2/3
Are there results?: Not yet: the study is under way

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

Who may be able to join

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

Who cannot join

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.

Show all 12Show fewer

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Bernardino Clavo, MD, PhD contact

34928449278

bernardinoclavo@gmail.com

Francisco Rodríguez-Esparragón, BSc, PhD contact

34928449288

afrodesp@gmail.com

Spain1 site, 1 recruiting

Dr. Negrín University Hospital
Las Palmas, Las Palmas, 35019
Bernardino Clavo, MD, PhD, 34928449278, bernardinoclavo@gmail.com
Francisco Rodríguez-Esparragón, BSc, PhD, 34928449288, afrodesp@gmail.com
Recruiting

Other trials in Spain

About this study

Official title: 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 main questions to answer are:

Can ozone therapy improve patients' self-perceived level of numbness and tingling?
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:

patients' self-perceived level of paresthesia
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:

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.
the evolution of the sensory neuropathy
the evolution of the level of anxiety and depression,
the evolution of biochemical parameters related to oxidative stress and chronic inflammation.
the evolution of hyperspectral signatures obtained from hands and feet.
to evaluate the toxicity of rectal ozone treatment in these patients.

Main trial endpoints.

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)
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).

Conditions: Chemotherapy Induced Peripheral Neuropathy (CIPN), Paresthesia, Numbness, Tingling
Being tested: Ozone therapy, Oxygen (placebo)
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
Medical subject headings: Paresthesia, Hypesthesia, Anxiety Disorders, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ozone therapyDrug
Also called Ozone treatment, O3, O3/O2 gas mixture
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.
Oxygen (placebo)Drug
Also called O2
Usual treatment (by their oncologist or hematologist) + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.

Study groups in NCT06706544
Study group	Role	What they receive
Ozone Group	Experimental	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. Receives: Drug: Ozone therapy
Oxygen Group (Placebo)	Placebo comparator	Drug: Oxygen (O2). Treatment: Usual treatment + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks. Receives: Drug: Oxygen (placebo)

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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).
Measured: 28 weeks

Secondary outcomes (20)

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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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
Measured: 16 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of ozone treatment.
Changes in serum levels of pro-inflammatory cytokines.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 28 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of follow-up.
Changes in serum levels of pro-inflammatory cytokines.
Measured: 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.
Measured: 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).
Measured: 28 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Feb 202531 Mar 2030

First posted26 Nov 2024
Study start7 Feb 2025
Primary completion31 Dec 2029 (estimated)
Study completion31 Mar 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (20)Papers the sponsor has linked to this study.
Other trials for Chemotherapy Induced Peripheral Neuropathy (CIPN)Studies 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: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized, triple-blind clinical trial
Masking: Triple blind
Who is masked: Participant, Care provider, Outcomes assessor
Enrolment: 42 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06706544
Sponsor's protocol ID: OzoParQT
Other IDs: PI23/01324, CIGC'23/24, 2024-517196-20-00, 2023-210-1
Acronym: OzoParQT
Status last verified: Sep 2026
First submitted: 22 Nov 2024
Last updated: 18 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: 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.

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

Interested in taking part?

Bernardino Clavo, MD, PhD

34928449278

bernardinoclavo@gmail.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT06706544
Acronym / sponsor ID: OzoParQT / OzoParQT
Conditions: 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
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 42 participants (estimated)
Lead sponsor: Bernardino Clavo, MD, PhDUniversity, hospital or other
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
Study start: 7 Feb 2025 (actual)
Primary completion: 31 Dec 2029 (estimated)
Study completion: 31 Mar 2030 (estimated)
First posted: 26 Nov 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The main questions to answer are:

Can ozone therapy improve patients' self-perceived level of numbness and tingling?
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.

Detailed description

Primary objectives:

patients' self-perceived level of paresthesia
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:

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.
the evolution of the sensory neuropathy
the evolution of the level of anxiety and depression,
the evolution of biochemical parameters related to oxidative stress and chronic inflammation.
the evolution of hyperspectral signatures obtained from hands and feet.
to evaluate the toxicity of rectal ozone treatment in these patients.

Main trial endpoints.

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)
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)

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, outcomes assessor)
Number of arms: 2
Model description: Randomized, triple-blind clinical trial

Arm	Type	Receives
Ozone Group	Experimental	Drug: Ozone therapyDrug: 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.
Oxygen Group (Placebo)	Placebo comparator	Drug: Oxygen (placebo)Drug: Oxygen (O2). Treatment: Usual treatment + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ozone therapyAlso: Ozone treatment, O3, O3/O2 gas mixtureUsual 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.	Drug	Ozone Group
Oxygen (placebo)Also: O2Usual treatment (by their oncologist or hematologist) + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.	Drug	Oxygen Group (Placebo)

Primary outcome

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)
Time frame: 28 weeks
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).
Change from Baseline in quality of life by the EQ-...
Time frame: 28 weeks
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).

20 secondary outcomes

Direct hospital costs
Time frame: 28 weeks
Change from baseline in "numbness and tingling" self-perceived by patients at the end of ozone treatment.
Time frame: 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.
Time frame: 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.
Time frame: 16 weeks.
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment.
Time frame: 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).
Time frame: 16 weeks.
Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire at the end of ozone treatment.
Time frame: 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.
Time frame: 16 weeks
Changes from baseline in biochemical parameters of oxidative stress at the end of ozone treatment.
Time frame: 16 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of ozone treatment.
Time frame: 16 weeks
Changes from baseline in Hyperspectral signatures and infrared images obtained from hands and feet at then of ozone treatment.
Time frame: 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.
Time frame: 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.
Time frame: 28 weeks
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of follow-up.
Time frame: Time frame: 28 weeks
Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire at the end of follow-up.
Time frame: 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.
Time frame: 28 weeks.
Changes from baseline in biochemical parameters of oxidative stress at the end of follow-up.
Time frame: 28 weeks.
Changes from baseline in biochemical parameters of inflammation at the end of follow-up.
Time frame: 28 weeks.
Changes from baseline in Hyperspectral signatures and infrared images obtained from hands and feet at the end of follow-up.
Time frame: 28 weeks.
Toxicity of rectal ozone treatment at the end of follow-up.
Time frame: 28 weeks.

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
Background: PubMed 34360655Viebahn-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.
Background: PubMed 34943049Tricarico 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.
Background: PubMed 36982352Szklener 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.
Background: PubMed 23549581Smith 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.
Background: PubMed 23046293Hidalgo-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.
Background: PubMed 35283802Hidalgo-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.
Background: PubMed 31426459Galie 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.
Background: PubMed 22105041Clavo 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.
Background: PubMed 31779159Clavo 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.
Background: PubMed 33738491Clavo 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.
Background: PubMed 32379556Clavo 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.
Background: PubMed 36111149Clavo 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.
Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Bernardino Clavo, MD, PhD contact

34928449278

bernardinoclavo@gmail.com

Francisco Rodríguez-Esparragón, BSc, PhD contact

34928449288

afrodesp@gmail.com

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ozone therapy in people with Chemotherapy Induced Peripheral Neuropathy (CIPN) and Paresthesia, run by Bernardino Clavo, MD, PhD at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bernardino Clavo, MD, PhD (34928449278, bernardinoclavo@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 28 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06706544, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.