A Phase 2/3 interventional study of Ozone and Oxygen in Chemotherapy-induced Peripheral Neuropathy, Pain, Neuropathic and Pain Syndrome, sponsored by Bernardino Clavo, MD, PhD. Recruiting at 2 sites in Spain. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Bernardino Clavo, MD, PhD · Phase 2/3, Interventional, and Treatment
The main objective of this clinical trial is to evaluate the effectiveness and cost-effectiveness of adding ozone therapy to the clinical management of patients with pain secondary to chemotherapy-induced peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a decrease and/or interruption of the chemotherapy treatment-limiting its effectiveness. The therapeutic measures for the CIPN are very limited in their number and efficacy.
Main Objectives: 1) To evaluate the clinical effect on the health-related quality of life (HRQOL) of adding ozone to the usual patient´s treatment with persistent pain because of CIPN. 2) Estimate the additional costs and evaluate the cost-effectiveness ratio.
Secondary Objectives: To evaluate the evolution of 3) oxidative stress and chronic inflammation through biochemical measurements; 4) anxiety and depression of patients; 5) the diagnostic and predictive value of hyperspectral imaging in the assessment of pain; 6) the acceptability of patients to a shared decision-making (SDM) tool.
METHODOLOGY: Randomized controlled trial (RCT) phase II-III, randomized, triple-blind; 42 patients with any kind of cancer treated with any kind of chemotherapy, with CIPN of grade > = 2 for > = 3 months.
TREATMENT: All patients will receive: usual treatment + 40 rectal insufflation sessions of O3/O2 in 16 weeks:
Main Variables: At the end of treatment with O3/O2 the following variables will be analyzed: 1) "average pain" secondary to CIPN following the Brief Pain Inventory-Short Form (BPI-SF); 2) health-related quality of life (HRQOL) and utilities using EQ-5D-5L and SF-36 quality of life questionnaires; 3) Direct costs.
Secondary Variables: 3) biochemical parameters of oxidative stress and inflammation; 4) Hamilton scale for anxiety and depression; 5) hyperspectral images; 6) acceptability of patients to a shared decision-making (SDM) tool.
Assessments at weeks: 0 (baseline), 16 (end of O3/O2 insufflations, objective), and 28 (end of follow-up, control).
Length of treatment: 16 weeks.
Follow-up: 12 weeks after finishing O3/O2 insufflation.
Planned length of the clinical trial: 36 months.
1,100 studies on the registry are indexed under Neuralgia; 241 are open to participants now.
This study's planned enrollment of 42 is below the median of 52 across 831 interventional studies indexed under Neuralgia.
Browse Neuralgia studies →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.
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.
Exclusion Criteria:
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.
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.
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.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
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.
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.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
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.
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.
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.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Ozone Ozone Group: Usual treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks. Other Names: O3
Drug: Ozone
Drug: Oxygen Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks. Other Names: O2
Drug: Oxygen
Ozone Group: Standard treatment + Ozone therapy (O3/O2) by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.
Also known as: O3
Control Group: Standard treatment + Oxygen (O2) by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.
Also known as: O2
Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at the end of ozone therapy)
Self-reported evaluation of 15 items to assess the severity of pain on daily functions in seven interference areas. From the 15 items, 11 items are scored from 0 ("No pain" or "Does not no interfere") to 10 ("Pain as bad as you can imagine" or "Completely interferes").
Time frame: 16 weeks
Direct Hospital Cost (at the end of ozone therapy)
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros).
Time frame: 16 weeks
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
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 extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine)
Time frame: 16 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36v2) questionnaire (at the end of ozone therapy)
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
Time frame: 16 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
Time frame: 16 weeks
Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
Serum levels of pro-inflammatory interleukins and TNFalpha
Time frame: 16 weeks
Change from Baseline in Hyperspectral image of painful area (at the end of ozone therapy)
Assessment of the percentage of reflectance for each wavelength
Time frame: 16 weeks
Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at the end of ozone therapy)
Clinician-administered depression assessment scale with 17 items pertaining to symptoms of depression experienced over the past week. Each item is scored from 0 (better, no alteration) to 2 (worse level of alteration) for items with three options, or from or from 0 (better, no alteration) to 4 (worse level of alteration) for items with five options. Overall score is from 0 (better, no anxiety/depression) to 52 (worse, very severe anxiety/depression).
Time frame: 16 weeks
Change from Baseline in Nerve conduction studies in the painful area (at the end of ozone therapy)
Assessment of nerve conduction velocity (in m/s)
Time frame: 16 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at the end of ozone therapy)
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
Time frame: 16 weeks
Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at 12 weeks after the end of ozone therapy)
Self-reported evaluation of 15 items to assess the severity of pain on daily functions in seven interference areas. From the 15 items, 11 items are scored from 0 ("No pain" or "Does not no interfere") to 10 ("Pain as bad as you can imagine" or "Completely interferes")
Time frame: 28 weeks
Direct Hospital Cost (at 12 weeks after the end of ozone therapy)
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros)
Time frame: 28 weeks
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at 12 weeks after the end of ozone therapy)
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 extreme problem or I am unable to…) and b) additional self-assessment of health by a visual analogue scale (0 = worst health patient can imagine, 100 = best health patient can imagine)
Time frame: 28 weeks
Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36v2) questionnaire (at 12 weeks after the end of ozone therapy)
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
Time frame: 28 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at 12 weeks after the end of ozone therapy)
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
Time frame: 28 weeks
Change from Baseline in Biochemical parameters of inflammation (at 12 weeks after the end of ozone therapy)
Serum levels of pro-inflammatory interleukins and TNFalpha
Time frame: 28 weeks
Change from Baseline in Hyperspectral image of painful area (at 12 weeks after the end of ozone therapy)
Assessment of the percentage of reflectance for each wavelength
Time frame: 28 weeks
Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at 12 weeks after the end of ozone therapy)
Clinician-administered depression assessment scale with 17 items pertaining to symptoms of depression experienced over the past week. Each item is scored from 0 (better, no alteration) to 2 (worse level of alteration) for items with three options, or from or from 0 (better, no alteration) to 4 (worse level of alteration) for items with five options. Overall score is from 0 (better, no anxiety/depression) to 52 (worse, very severe anxiety/depression)
Time frame: 28 weeks
Change from Baseline in Nerve conduction studies in the painful area (at 12 weeks after the end of ozone therapy)
Assessment of nerve conduction velocity (in m/s)
Time frame: 28 weeks
Incidence of severe adverse events in accordance with the definition of the Council for International Organizations of Medical Sciences (at 12 weeks after the end of ozone therapy)
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
Time frame: 28 weeks
Plan to share: No
Started Nov 2020 (actual). Primary completion is estimated for Sep 2027, 82 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Ozone
Bernardino Clavo, MD, PhD