Ozone Therapy in Chemotherapy-induced Peripheral Neuropathy: RCT (O3NPIQ) (O3NPIQ)

March 1, 2024 updated by: Bernardino Clavo, MD, PhD

Effectiveness and Cost-effectiveness of Ozone Therapy in Patients With Pain Secondary to Chemotherapy-induced Peripheral Neuropathy. Randomized, Triple-blind Clinical Trial (O3NPIQ)

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

Study Overview

Detailed Description

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:

  • Ozone-Arm (n = 21): concentration of O3/O2 increasing from 10 to 30 μg/ml.
  • Control-placebo- Arm (n = 21): concentration of O3/O2 = 0 μg/ml.

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.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Las Palmas
      • Las Palmas De Gran Canaria, Las Palmas, Spain, 35016
        • Recruiting
        • Complejo Hospitalario Materno Insular
        • Contact:
      • Las Palmas De Gran Canaria, Las Palmas, Spain, 35019
        • Recruiting
        • Hospital Universitario de Gran Canaria Dr. Negrin
        • Contact:
        • Sub-Investigator:
          • Saray Galván, MD
        • Sub-Investigator:
          • Francisco Rodríguez-Esparragón, BSc, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Adults > = 18 years old.
  • 2. Any kind of cancer in any stage, treated with any kind of chemotherapy, and life expectancy > = 6 months.
  • 3. Clinical diagnosis of painful chemotherapy-induced peripheral neuropathy, toxicity Grade 2 or higher according to the Common Toxicity Criteria for Adverse Events (CTCAE) from the National Cancer Institute of EEUU, v.5.0, for > = 3 months and without the inclusion of new treatments for pain and/or neuropathy for > = 1 month.
  • 4. "Average pain" > = 3/10 according to the Brief Pain Inventory-Short Form (BPI-SF) > = 3 months beyond chemotherapy completion.
  • 5. Pregnant women cannot participate in the clinical trial.
  • 6. 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 the 14 days prior to the first ozone therapy session up to 14 days after the last one.
  • 7. Patients who have signed and dated the study 's specific informed consent

Exclusion Criteria:

  • 1. Age < 18 years old.
  • 2. Pregnancy at the time of enrollment.
  • 3. Women with childbearing potential who are unwilling to perform a pregnancy test and/or employ adequate contraception from the 14 days prior to the first ozone therapy session up to 14 days after the last one.
  • 4. Clinical suspicion that peripheral neuropathy (compressive or diabetic neuropathy) in the same area prior to receiving neurotoxic chemotherapy.
  • 5. Psychiatric illness or social situations that would limit compliance with study requirements.
  • 6. Those who are unable to fill in the scales used to measure quality of life variables
  • 7. Specific liver enzymes [Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) > 5 times the upper limit of normal
  • 8. Increased creatinine > 3 times the upper limit of normal.
  • 9. Hemodynamically or clinically unstable patients or uncontrolled severe illness.
  • 10. Uncontrolled cancer disease.
  • 11. Leptomeningeal carcinomatosis.
  • 12. Life expectancy < 6 months
  • 13. Contraindication or disability for rectal ozone administration or to attend scheduled treatments.
  • 14. Known allergy to ozone.
  • 15.Patients who do not meet all the inclusion criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ozone Group

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

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.
Other Names:
  • O3
Placebo Comparator: Control Group

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at the end of ozone therapy)
Time Frame: 16 weeks
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").
16 weeks
Direct Hospital Cost (at the end of ozone therapy)
Time Frame: 16 weeks
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros).
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
Time Frame: 16 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 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)
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)
Time Frame: 16 weeks
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
16 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
Time Frame: 16 weeks
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
16 weeks
Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
Time Frame: 16 weeks
Serum levels of pro-inflammatory interleukins and TNFalpha
16 weeks
Change from Baseline in Hyperspectral image of painful area (at the end of ozone therapy)
Time Frame: 16 weeks
Assessment of the percentage of reflectance for each wavelength
16 weeks
Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at the end of ozone therapy)
Time Frame: 16 weeks
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).
16 weeks
Change from Baseline in Nerve conduction studies in the painful area (at the end of ozone therapy)
Time Frame: 16 weeks
Assessment of nerve conduction velocity (in m/s)
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)
Time Frame: 16 weeks
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
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)
Time Frame: 28 weeks
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")
28 weeks
Direct Hospital Cost (at 12 weeks after the end of ozone therapy)
Time Frame: 28 weeks
The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 16 weeks of ozone therapy (in euros)
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)
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 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)
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)
Time Frame: 28 weeks
Self-reported evaluation of 36 items (0 = worst, 100 = best). Final accumulated total range from 0 (worst) to 100 (best)
28 weeks
Change from Baseline in Biochemical parameters of oxidative stress (at 12 weeks after the end of ozone therapy)
Time Frame: 28 weeks
Serum levels of superoxide dismutase, glutathione, glutathione peroxidase and free radicals
28 weeks
Change from Baseline in Biochemical parameters of inflammation (at 12 weeks after the end of ozone therapy)
Time Frame: 28 weeks
Serum levels of pro-inflammatory interleukins and TNFalpha
28 weeks
Change from Baseline in Hyperspectral image of painful area (at 12 weeks after the end of ozone therapy)
Time Frame: 28 weeks
Assessment of the percentage of reflectance for each wavelength
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)
Time Frame: 28 weeks
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)
28 weeks
Change from Baseline in Nerve conduction studies in the painful area (at 12 weeks after the end of ozone therapy)
Time Frame: 28 weeks
Assessment of nerve conduction velocity (in m/s)
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)
Time Frame: 28 weeks
Number of events that are fatal, life threatening, leading to or prolonging a stay in hospital, or resulting in severe disability
28 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Bernardino Clavo, MD, PhD, Dr. Negrín University Hospital, Las Palmas, Spain
  • Study Director: Pedro G Serrano-Aguilar, MD, PhD, Servicio de Evaluación. Servicio Canario de Salud. Spain
  • Principal Investigator: Delvys Rodríguez-Abreu, MD, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas, Spain
  • Principal Investigator: Gustavo M Callico, Prof, PhD, Institute for Applied Microelectronics, University of Las Palmas de G. C., Spain
  • Principal Investigator: Francisco Rodríguez-Esparragón, BSc, PhD, Dr. Negrín University Hospital, Las Palmas, Spain
  • Principal Investigator: Bernardino Clavo, MD, PhD, Dr. Negrín University Hospital, Las Palmas, Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2020

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 5, 2020

First Submitted That Met QC Criteria

March 6, 2020

First Posted (Actual)

March 9, 2020

Study Record Updates

Last Update Posted (Estimated)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • O3NPIQ
  • 2019-000821-37 (Other Identifier: Registro Español de Estudios Clínicos (REec))
  • PI 19/00458 (Other Grant/Funding Number: Instituto de Salud Carlos III)
  • 016/2019 (Other Grant/Funding Number: Fundación DISA)
  • BF1-19-03 (Other Grant/Funding Number: Fundación Española del Dolor (FED))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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