Clinical trial NCT04299893: Ozone Therapy in Chemotherapy-induced Peripheral Neuropathy: RCT (O3NPIQ)
Official title: Effectiveness and Cost-effectiveness of Ozone Therapy in Patients With Pain Secondary to Chemotherapy-induced Peripheral Neuropathy. Randomized, Triple-blind Clinical Trial (O3NPIQ)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Chemotherapy-induced Peripheral Neuropathy
Pain, Neuropathic
Pain Syndrome
Keywords: complementary and integrative medicine
cost-effectiveness ratio
chemotherapy-induced peripheral neuropathy
pain
ozone therapy
quality of life related to health
shared decision-making tool
randomized controlled trial
Lead sponsor: Dr. Negrin University Hospital
Sponsor class: OTHER
Collaborators: name: Servicio Canario de Salud
name: Instituto de Salud Carlos III
name: Red de Investigación en Servicios de Salud en Enfermedades Crónicas
name: Fundación DISA, Spain
name: Fundación Española del Dolor (FED)
First posted: 2020-03-09
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Standard treatment + ozone therapy (O3/O2) versus Standard treatment + oxygen (O2) as placebo
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in "Average pain" according to the Brief Pain Inventory-Short Form (BPI-SF) (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Direct Hospital Cost (at the end of ozone therapy)
timeFrame: 16 weeks
Secondary outcomes:
measure: Change from Baseline in quality of life by the "5-level, 5-dimension EuroQol" (EQ-5D-5L) questionnaire (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in quality of life by the "Short Form 36-item health survey" (SF-36v2) questionnaire (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in Biochemical parameters of oxidative stress (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in Biochemical parameters of inflammation (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in Hyperspectral image of painful area (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at the end of ozone therapy)
timeFrame: 16 weeks
measure: Change from Baseline in Nerve conduction studies in the painful area (at the end of ozone therapy)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: 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)
timeFrame: 28 weeks
measure: Direct Hospital Cost (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: 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)
timeFrame: 28 weeks
measure: 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)
timeFrame: 28 weeks
measure: Change from Baseline in Biochemical parameters of oxidative stress (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: Change from Baseline in Biochemical parameters of inflammation (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: Change from Baseline in Hyperspectral image of painful area (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: Change from Baseline in Levels of anxiety and depression according to the Hamilton scale (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: Change from Baseline in Nerve conduction studies in the painful area (at 12 weeks after the end of ozone therapy)
timeFrame: 28 weeks
measure: 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)
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Las Palmas De Gran Canaria
country: Spain
facility: Complejo Hospitalario Materno Insular
state: Las Palmas
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrín
state: Las Palmas
Study officials:
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Bernardino Clavo, MD, PhD
role: STUDY_CHAIR
affiliation: Servicio de Evaluación. Servicio Canario de Salud. Spain
name: Pedro G Serrano-Aguilar, MD, PhD
role: STUDY_DIRECTOR
affiliation: Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas, Spain
name: Delvys Rodríguez-Abreu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute for Applied Microelectronics, University of Las Palmas de G. C., Spain
name: Gustavo M Callico, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Francisco Rodríguez-Esparragón, BSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dr. Negrín University Hospital, Las Palmas, Spain
name: Bernardino Clavo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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