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

Bernardino Clavo, MD, PhD

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Chemotherapy-induced Peripheral Neuropathy; Pain Syndrome; Pain, Neuropathic

Treatments: Drug: Oxygen; Drug: Ozone

Study type: Interventional

Funder types: Other

Identifiers

NCT04299893

BF1-19-03 (Other Grant/Funding Number)

016/2019 (Other Grant/Funding Number)

2019-000821-37 (EudraCT Number)

PI 19/00458 (Other Grant/Funding Number)

2018-156-1

Details and patient eligibility

About

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

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

42 participants in 2 patient groups, including a placebo group

Ozone Group

Experimental group

Description:

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

Treatment:

Drug: Ozone

Control Group

Placebo Comparator group

Description:

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

Treatment:

Drug: Oxygen