Chemotherapy Induced Peripheral Neuropathy (CIPN)Phase 2/3OzoParQTmicrobNCT06799351
Gut Microbiome Profiles in Patients With Chemotherapy-induced Neuropathy in the RCT OzoParQT (NCT06706544).
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.
Trial summary
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life. 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
- 0. Patients who agree to participate in the randomized clinical trial OzoParQT, and who also agree to participate in this study of gut microbiota by providing stool samples.
- 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.
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- 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 specific informed consent of both studies (OzoParQT and OzoParQTmicrob)
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.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC)
Las Palmas, Las Palmas, 35019
Bernardino Clavo, MD, PhD, 34928449278, bernardinoclavo@gmail.com
Francisco Rodríguez-Esparragón, BSc, PhD, 34928449288, afrodesp@gmail.com
About this study
Official title: Evaluation of the Gut Microbiome Profiles in Patients With Chemotherapy-induced Peripheral Neuropathy Treated in the Randomized Clinical Trial With Ozone OzoParQT (NCT06706544).
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life.
Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response.
Read more
This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy.
Primary Objectives:
To evaluate if gut microbiome profiles differ between patients:
- with and without symptomatic improvement of CIPN.
- receiving rectal ozone therapy and those receiving placebo.
Secondary Objectives:
To evaluate the relationship between gut microbiome composition and:
- Health-related quality of life,
- Anxiety and depression,
- Biochemical markers of oxidative stress and inflammation.
Main Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Gut microbiome profile
- Patient-reported numbness and tingling
- Neuropathy severity (QLQ-CIPN20 scale)
- Paresthesia toxicity grade (CTCAE v.5.0)
Secondary Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Patient-reported quality of life (EQ-5D-5L questionnaire)
- Quality of life (QLQ-C30 questionnaire)
- Anxiety and depression levels (HADS questionnaire)
- Biochemical markers of oxidative stress
- Biochemical markers of inflammation
Trial Design:
This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
Trial Population in the OzoParQT trial (NCT06706544):
Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months.
Intervention in the OzoParQT trial (NCT06706544).
All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks:
- Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
- Control-placebo group: O2 only (0 µg/mL O3)
Study Duration:
Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.
Read the detailed description
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life.
Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response.
This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy.
Primary Objectives:
To evaluate if gut microbiome profiles differ between patients:
- with and without symptomatic improvement of CIPN.
- receiving rectal ozone therapy and those receiving placebo.
Secondary Objectives:
To evaluate the relationship between gut microbiome composition and:
- Health-related quality of life,
- Anxiety and depression,
- Biochemical markers of oxidative stress and inflammation.
Main Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Gut microbiome profile
- Patient-reported numbness and tingling
- Neuropathy severity (QLQ-CIPN20 scale)
- Paresthesia toxicity grade (CTCAE v.5.0)
Secondary Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Patient-reported quality of life (EQ-5D-5L questionnaire)
- Quality of life (QLQ-C30 questionnaire)
- Anxiety and depression levels (HADS questionnaire)
- Biochemical markers of oxidative stress
- Biochemical markers of inflammation
Trial Design:
This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
Trial Population in the OzoParQT trial (NCT06706544):
Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months.
Intervention in the OzoParQT trial (NCT06706544).
All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks:
- Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
- Control-placebo group: O2 only (0 µg/mL O3)
Study Duration:
Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.
- 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, oxidative stress, gut microbiota
- 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/O2 gas mixture, O3
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 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 gut microbiome profile, at the end of ozone therapy.
Analysis of gut microbiome profile at the end of ozone therapy regarding the basal profile.
Measured: 16 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 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 grouped into 3 dimensions: sensory, 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 100, with 0 being the best possible state and 100 being the worst.
Measured: 16 weeks.
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.
Secondary outcomes (5)
Change from baseline in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients at the end 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2025
- 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 (18)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
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bernardino Clavo, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Instituto de Salud Carlos III, Council of Gran Canaria, Centers for International Business Education and Research, Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna
- Responsible party
- Sponsor-investigator, Bernardino Clavo, MD, PhD, Hospital Universitario de Gran Canaria Doctor Negrín
- Investigators
- Bernardino Clavo, MD, PhD, Study chair, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, SpainFrancisco Rodríguez-Esparragón, BSc, PhD, Study director, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, SpainJacob Lorenzo-Morales, Prof, Principal investigator, Instituto Universitario de Enfermedades Tropicales y Salud Publica de Canarias - Universidad de La Laguna (IUETSPC-ULL)Francisco Rodríguez-Esparragón, BSc, PhD, Principal investigator, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, SpainBernardino Clavo, MD, PhD, Principal investigator, Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06799351
- Sponsor's protocol ID
- 2024-385-1
- Other IDs
- PIFIISC24/37, PI23/01324, CIGC'23/24
- Acronym
- OzoParQTmicrob
- Status last verified
- Sep 2026
- First submitted
- 23 Jan 2025
- Last updated
- 25 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
Ramakrishna C, Corleto J, Ruegger PM, Logan GD, Peacock BB, Mendonca S, Yamaki S, Adamson T, Ermel R, McKemy D, Borneman J, Cantin EM. Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain. Sci Rep. 2019 Dec 30;9(1):20324. doi: 10.1038/s41598-019-56832-x.
PubMed 31889131Lin B, Wang Y, Zhang P, Yuan Y, Zhang Y, Chen G. Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain. 2020 Aug 17;21(1):103. doi: 10.1186/s10194-020-01170-x.
PubMed 32807072Clavo B, Rodriguez-Abreu D, Galvan-Ruiz S, Federico M, Canovas-Molina A, Ramallo-Farina Y, Antonilli C, Benitez G, Fabelo H, Garcia-Lourve C, Gonzalez-Beltran D, Jorge IJ, Rodriguez-Esparragon F, Callico GM. Long-Term Effects of Ozone Treatment in Patients with Persistent Numbness and Tingling Secondary to Chemotherapy-Induced Peripheral Neuropathy. A Retrospective Study. Integr Cancer Ther. 2025 Jan-Dec;24:15347354241307038. doi: 10.1177/15347354241307038.
PubMed 39797612Bocci 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 19260079Bocci 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 25699252Bocci 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 21575276Clavo 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 37599784Clavo 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 36674232Clavo 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 33802143Clavo 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 36111149Clavo 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 32379556Clavo 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 33738491Clavo 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 31779159Galie 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 31426459Hidalgo-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
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Gut Microbiome Profiles in Patients With Chemotherapy-induced Peripheral Neuropathy Treated in the Randomized Clinical Trial With Ozone OzoParQT (NCT06706544).
- ClinicalTrials.gov ID
- NCT06799351
- Acronym / sponsor ID
- OzoParQTmicrob / 2024-385-1
- 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
- Fundación Canaria Instituto de Investigación Sanitaria de Canarias, Instituto de Salud Carlos III, Council of Gran Canaria, Centers for International Business Education and Research, Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna
- Study start
- 7 Feb 2025 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 29 Jan 2025 (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.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life.
Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response.
This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy.
Primary Objectives:
To evaluate if gut microbiome profiles differ between patients:
- with and without symptomatic improvement of CIPN.
- receiving rectal ozone therapy and those receiving placebo.
Secondary Objectives:
To evaluate the relationship between gut microbiome composition and:
- Health-related quality of life,
- Anxiety and depression,
- Biochemical markers of oxidative stress and inflammation.
Main Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Gut microbiome profile
- Patient-reported numbness and tingling
- Neuropathy severity (QLQ-CIPN20 scale)
- Paresthesia toxicity grade (CTCAE v.5.0)
Secondary Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Patient-reported quality of life (EQ-5D-5L questionnaire)
- Quality of life (QLQ-C30 questionnaire)
- Anxiety and depression levels (HADS questionnaire)
- Biochemical markers of oxidative stress
- Biochemical markers of inflammation
Trial Design:
This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
Trial Population in the OzoParQT trial (NCT06706544):
Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months.
Intervention in the OzoParQT trial (NCT06706544).
All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks:
- Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
- Control-placebo group: O2 only (0 µg/mL O3)
Study Duration:
Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.
Detailed description
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life.
Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response.
This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy.
Primary Objectives:
To evaluate if gut microbiome profiles differ between patients:
- with and without symptomatic improvement of CIPN.
- receiving rectal ozone therapy and those receiving placebo.
Secondary Objectives:
To evaluate the relationship between gut microbiome composition and:
- Health-related quality of life,
- Anxiety and depression,
- Biochemical markers of oxidative stress and inflammation.
Main Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Gut microbiome profile
- Patient-reported numbness and tingling
- Neuropathy severity (QLQ-CIPN20 scale)
- Paresthesia toxicity grade (CTCAE v.5.0)
Secondary Trial Endpoints.
Changes from baseline at the end of ozone therapy (week 16) in:
- Patient-reported quality of life (EQ-5D-5L questionnaire)
- Quality of life (QLQ-C30 questionnaire)
- Anxiety and depression levels (HADS questionnaire)
- Biochemical markers of oxidative stress
- Biochemical markers of inflammation
Trial Design:
This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
Trial Population in the OzoParQT trial (NCT06706544):
Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months.
Intervention in the OzoParQT trial (NCT06706544).
All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks:
- Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
- Control-placebo group: O2 only (0 µg/mL O3)
Study Duration:
Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).
| 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 (9 listed)
- 0. Patients who agree to participate in the randomized clinical trial OzoParQT, and who also agree to participate in this study of gut microbiota by providing stool samples.
- 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.
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/O2 gas mixture, O3Usual 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 gut microbiome profile, at the end of ozone therapy.
Time frame: 16 weeks.
Analysis of gut microbiome profile at the end of ozone therapy regarding the basal profile.
Change from baseline in "numbness and tingling" self-perceived by patients at the end of ozone treatment.
Time frame: 16 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).
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 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 (from the European Organization for Research \& Treatment in Cancer (EORTC)). It is evaluated through 20 items grouped into 3 dimensions: sensory, 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 100, with 0 being the best possible state and 100 being the worst.
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 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).
5 secondary outcomes
Change from baseline in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients at the end 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.
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 25 Sep 2026.
- Background: PubMed 31889131Ramakrishna C, Corleto J, Ruegger PM, Logan GD, Peacock BB, Mendonca S, Yamaki S, Adamson T, Ermel R, McKemy D, Borneman J, Cantin EM. Dominant Role of the Gut Microbiota in Chemotherapy Induced Neuropathic Pain. Sci Rep. 2019 Dec 30;9(1):20324. doi: 10.1038/s41598-019-56832-x.
- Background: PubMed 32807072Lin B, Wang Y, Zhang P, Yuan Y, Zhang Y, Chen G. Gut microbiota regulates neuropathic pain: potential mechanisms and therapeutic strategy. J Headache Pain. 2020 Aug 17;21(1):103. doi: 10.1186/s10194-020-01170-x.
- Background: PubMed 39797612Clavo B, Rodriguez-Abreu D, Galvan-Ruiz S, Federico M, Canovas-Molina A, Ramallo-Farina Y, Antonilli C, Benitez G, Fabelo H, Garcia-Lourve C, Gonzalez-Beltran D, Jorge IJ, Rodriguez-Esparragon F, Callico GM. Long-Term Effects of Ozone Treatment in Patients with Persistent Numbness and Tingling Secondary to Chemotherapy-Induced Peripheral Neuropathy. A Retrospective Study. Integr Cancer Ther. 2025 Jan-Dec;24:15347354241307038. doi: 10.1177/15347354241307038.
- Background: PubMed 19260079Bocci 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.
- Background: PubMed 25699252Bocci 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.
- Background: PubMed 21575276Bocci 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.
- Background: PubMed 37599784Clavo 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.
- Background: PubMed 36674232Clavo 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.
- Background: PubMed 33802143Clavo 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.
- 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.
- 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 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.
- 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 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
Jacob Lorenzo-Morales, Prof principal investigator
Instituto Universitario de Enfermedades Tropicales y Salud Publica de Canarias - Universidad de La Laguna (IUETSPC-ULL)
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 9 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 25 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 gut microbiome profile, at the end of ozone therapy. (time frame: 16 weeks.). The study lists 4 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 NCT06799351, which also lists 18 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 25 Sep 2026.