Ozone treatment in patients with numbness and/or tingling secondary to chemotherapy. Randomized clinical trial.

2024-517196-20-00 Protocol OzoParQT Phase II and Phase III (Integrated) Ongoing, recruiting

Start 7 Feb 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol OzoParQT

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)
Status Ongoing, recruiting
Participants planned 42
Countries 1
Sites 1

Paresthesia (numbness, tingling) secondary to chemotherapy-induced neuropathy.

To evaluate the effect of adding ozone to the usual management of patients with paresthesia (numbness and/or tingling) due to chemotherapy-induced peripheral neuropathy (CIPN), Grade 2 (moderate symptoms and/or limitation in instrumental activities of daily living) or higher, on: 1) patients' self-perceived level of pa…

Key facts

Sponsor
El Hospital Universitario De Gran Canaria Dr. Negrin
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Nervous System Diseases [C10]
Trial duration
7 Feb 2025 → ongoing
Decision date (initial)
2024-11-20
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation (and ERDF) · Cabildo de Gran Canaria, Las Palmas, Spain

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the effect of adding ozone to the usual management of patients with paresthesia (numbness and/or tingling) due to chemotherapy-induced peripheral neuropathy (CIPN), Grade 2 (moderate symptoms and/or limitation in instrumental activities of daily living) or higher, on:
1) patients' self-perceived level of paresthesia
2) patients' self-perceived health-related quality of life (HRQoL).

Secondary objectives 6

  1. the additional direct costs incurred in the application of ozone and evaluate the cost-effectiveness of the administration of ozone in these patients in comparison with the usual exclusive treatment.
  2. the evolution of the sensory neuropathy
  3. the evolution of the level of anxiety and depression,
  4. the evolution of biochemical parameters related to oxidative stress and chronic inflammation.
  5. the evolution of hyperspectral signatures obtained from hands and feet
  6. to evaluate the toxicity of rectal ozone treatment in these patients.

Conditions and MedDRA coding

Paresthesia (numbness, tingling) secondary to chemotherapy-induced neuropathy.

VersionLevelCodeTermSystem organ class
21.1 LLT 10043876 Tingling 10029205
21.1 LLT 10033987 Paresthesia 10029205
21.1 LLT 10029829 Numbness 10029205
20.1 LLT 10079545 Chemotherapy induced peripheral neuropathy 10029205

Study design 2 periods

#TitleAllocationBlindingRoles blindedArms
1 Ozone treatment in paresthesia secondary to chemotherapy-induced peripheral neuropathy (CIPN).
Effectiveness and cost-effectiveness of ozone treatment in patients with paresthesia (numbness, tingling) secondary to chemotherapy-induced peripheral neuropathy. Randomized, triple-blind clinical trial (OzoParQT).
 Randomised Controlled Double [{"id":93062,"code":1,"name":"Subject"},{"id":93063,"code":4,"name":"Analyst"},{"id":93064,"code":5,"name":"Carer"},{"id":93065,"code":3,"name":"Monitor"}] Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
Control-placebo group: O3/O2 concentration = 0 µg/mL
2 Ozone treatment in numbness and tingling secondary to chemotherapy-induced peripheral neuropathy
To evaluate the effect of adding ozone to the usual management of patients with paresthesia (numbness and/or tingling) due to chemotherapy-induced peripheral neuropathy (CIPN), Grade 2 (moderate symptoms and/or limitation in instrumental activities of daily living) or higher, on: 1. patients' self-perceived level of paresthesia 2. patients' self-perceived health-related quality of life (HRQoL). Secondary objectives: To evaluate (in patients with numbness and/or tingling secondary to CIPN) the effect of adding ozone to the usual management on: 1. the additional direct costs incurred in the application of ozone and evaluate the cost-effectiveness of the administration of ozone in these patients in comparison with the usual exclusive treatment. 2. the evolution of the sensory neuropathy 3. the evolution of the level of anxiety and depression, 4. the evolution of biochemical parameters related to oxidative stress and chronic inflammation. 5. the evolution of hyperspectral signatures obtained from hands and feet. 6. to evaluate the toxicity of rectal ozone treatment in these patients.
 Randomised Controlled Double [{"id":93068,"code":5,"name":"Carer"},{"id":93067,"code":1,"name":"Subject"},{"id":93069,"code":4,"name":"Analyst"}] Ozone group:: This arm will receive the usual treatment + 40 sessions of rectal insufflation of O3/O2 in 16 weeks, with O3/O2 concentration increasing from 10 to 30 µg/ml
Control/placebo group: This arm will receive the usual treatment + 40 sessions of rectal insufflation of O3/O2 in 16 weeks, with O3/O2 concentration of 0 µg/ml (that is, only O2)

Regulatory references

Plan to share IPD
Yes
IPD plan description
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: [email protected] To gain access, data requestors will need to sign a data access agreement.
EU CT numberTitleSponsor
2024-518021-16-00 Effectiveness and cost-effectiveness of Ozone therapy in patients with pain secondary to chemotherapy-induced peripheral neuropathy. Randomized, triple-blind clinical trial. Dr. Bernardino Clavo Varas

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  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 stable or in remission.
  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 the 14 days prior to the first ozone therapy session up to 14 days after the last one.
  8. To sign and date the study specific informed consent

Exclusion criteria 12

  1. Age < 18 years.
  2. A woman who is lactating, pregnant, suspected of being pregnant, or who is of childbearing age and 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.
  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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Change from Baseline in “paresthesia” (numbness, tingling) self perceived by patients (at the end of follow-up). Self-reported evaluation of the percentage in “Numbness" and/or “Tingling” regarding the basal level. From 100% (basal level, 0% improvement) to 0% (no numbness or tingling, 100% improvement). [Time Frame: 28 weeks]
  2. Change from Baseline in quality of life by the EQ-5D-5L questionnaire (from EuroQol), (at the end of follow-up) 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]

Secondary endpoints 20

  1. Direct Hospital Cost The direct expenses incurred by the hospital in providing services (medication, tests, medical visits...) during the 28 weeks of the study (in euros). [Time Frame: 28 weeks].
  2. Change from Baseline in “paresthesia” (numbness, tingling) self-perceived by patients (at the end of ozone treatment). Self-reported evaluation of the percentage in “Numbness" and/or “Tingling” regarding the basal level. From 100% (basal level, 0% improvement) to 0% (no numbness or tingling, 100% improvement). [Time Frame: 16 weeks]
  3. 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). (at the end of ozone treatment). Range from: Grade 0 (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities daily life) [Time Frame: 16 weeks]
  4. Changes from Baseline in the grade of toxicity of sensory neuropathy according to the CTCAE v.5.0 scale (from the National Cancer Institute of EEUU). (at the end of ozone treatment). Range from: Grade 0 (asymptomatic or mild symptoms) to Grade 4 (life-threatening consequences; urgent intervention indicated) [Time Frame: 16 weeks]
  5. Changes from Baseline in the degree of neuropathy according to the QLQ-CIPN20 scale (from the European Organization for Research & Treatment in Cancer (EORTC)). (at the end of ozone treatment). It is evaluated through 20 items that are grouped into 3 dimensions: sensitive, 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 scale from 0 to 100, being 0 the best state and 100 the worst. [Time Frame: 16 weeks]
  6. Change from Baseline in quality of life by the EQ-5D-5L questionnaire (from EuroQol), (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 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]
  7. Change from Baseline in quality of life by the QLQ-C30 questionnaire (EORTC), (at the end of ozone treatment) 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 function, worst for symptoms). Time Frame: 16 weeks]
  8. Change from Baseline in Levels of anxiety and depression according to the “HAD scale” (at the end of ozone treatment) HAD scale is a self-administered questionnaire which 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, overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression). [Time Frame: 16 weeks]
  9. Changes from Baseline in biochemical parameters of oxidative stress (at the end of ozone treatment). Serum levels of biochemical parameters of oxidative stress. (at the end of ozone treatment). [Time Frame: 16 weeks]
  10. Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy) (at the end of ozone treatment). Serum levels of pro-inflammatory cytokines [Time Frame: 16 weeks]
  11. Change from Baseline in Hyperspectral Image (HSI) of hands and feet (at the end of ozone treatment) Assessment of the percentage of reflectance for each wavelength [Time Frame: 16 weeks]
  12. 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). (at the end of follow-up). Range from: Grade 0 (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities daily life) [Time Frame: 28 weeks]
  13. Changes from Baseline in the grade of toxicity of sensory neuropathy according to the CTCAE v.5.0 scale (from the National Cancer Institute of EEUU). (at the end of follow-up). Range from: Grade 0 (asymptomatic or mild symptoms) to Grade 4 (life-threatening consequences; urgent intervention indicated) [Time Frame: 28 weeks]
  14. Changes from Baseline in the degree of neuropathy according to the QLQ-CIPN20 scale (from the European Organization for Research & Treatment in Cancer (EORTC)). (at the end of follow-up). It is evaluated through 20 items that are grouped into 3 dimensions: sensitive, 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 scale from 0 to 100, being 0 the best state and 100 the worst. [Time Frame: 28 weeks]
  15. Change from Baseline in quality of life by the QLQ-C30 questionnaire (EORTC), (at the end of follow-up) 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 function, worst for symptoms). Time Frame: 28 weeks]
  16. Change from Baseline in Levels of anxiety and depression according to the “HAD scale” (at the end of follow-up) HAD scale is a self-administered questionnaire which 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, overall score is from 0 (better, no anxiety or depression) to 21 (worse, very severe anxiety or depression). [Time Frame: 28 weeks]
  17. Changes from Baseline in biochemical parameters of oxidative stress (at the end of ozone treatment). Serum levels of biochemical parameters of oxidative stress. (at the end of follow-up). [Time Frame: 28 weeks]
  18. Changes from Baseline in biochemical parameters of inflammation (if systemic ozone therapy) (at the end of follow-up). Serum levels of pro-inflammatory cytokines [Time Frame: 28 weeks]
  19. Change from Baseline in Hyperspectral Image (HIS) of hands and feet (at the end of follow-up) Assessment of the percentage of reflectance for each wavelength [Time Frame: 28 weeks]
  20. Toxicity of rectal ozone therapy in these patients. at the end of follow-up. [Time Frame: 28 weeks]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Oxígeno Medicinal Gas Carburos Metálicos, 99.5% v/v gas comprimido medicinal

PRD321402 · Product

Active substance
Oxygen
Pharmaceutical form
MEDICINAL GAS, COMPRESSED
Route of administration
RECTAL USE
Max daily dose
9000 µg microgram(s)
Max total dose
360 mg milligram(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
V03AN01 — -
Marketing authorisation
66969
MA holder
S.E. CARBUROS METÁLICOS, S.A.
MA country
Spain
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Ozone will be obtained from O2 using an Ozone generator device with CE mark. - The obtained O3/O2 gas mixture will contain: < 5% of O3 (according to the selected concentration) and > 95% of O2. - At the specified volume, the obtained gas mixture will be insufflated by rectum, which is an unauthorized route for oxygen.

Placebo 1

Oxygen (by rectal insufflation)

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
Route of administration
RECTAL USE
Max daily dose
300 ml millilitre(s)
Max total dose
12000 ml millilitre(s)
Max treatment duration
16 Week(s)
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

El Hospital Universitario De Gran Canaria Dr. Negrin

Sponsor organisation
El Hospital Universitario De Gran Canaria Dr. Negrin
Address
Barranco De La Ballena S N
City
Las Palmas De Gran Canaria
Postcode
35010
Country
Spain

Scientific contact point

Organisation
El Hospital Universitario De Gran Canaria Dr. Negrin
Contact name
Bernardino Clavo Varas

Public contact point

Organisation
El Hospital Universitario De Gran Canaria Dr. Negrin
Contact name
Bernardino Clavo Varas

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Spain Ongoing, recruiting 42 1
Rest of world — 0 —

Investigational sites

Spain

1 site · Ongoing, recruiting
El Hospital Universitario De Gran Canaria Dr. Negrin
Research Unit, Chronic Pain Unit, Radiation Oncology Department, Barranco De La Ballena S N, 35010, Las Palmas De Gran Canaria

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Spain 2025-02-07 2025-02-07

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-517196-20-00 1
Protocol (for publication) D1_Protocol_tracked_changes_2024-517196-20-00 1
Protocol (for publication) Protocol_OzoParQT_English_2024_07_01 1
Recruitment arrangements (for publication) Recruitment_arrangements 1
Subject information and informed consent form (for publication) Hoja_Informacion_al_Paciente_y_Consentimiento_Informado 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_O3_O2_Tracked_changes 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_Oxygen_AEMPS 1
Summary of Product Characteristics (SmPC) (for publication) SmPC_Summary_of_Product_Characterstics_2024_06_21 1
Synopsis of the protocol (for publication) D1_Protocol_Synopsis_English_2024-517196-20-00 1
Synopsis of the protocol (for publication) D1_Protocol_Synopsis_Spanish_2024-517196-20-00 1
Synopsis of the protocol (for publication) Synopsis_protocol_Espanol_English 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-09 Spain Acceptable
2024-11-14
 2024-11-20