Gut Microbiome Profiles in Patients with Chemotherapy-induced Neuropathy in the RCT OzoParQT (NCT06706544).

Summary

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life.

Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response.

This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy.

Primary Objectives:

To evaluate if gut microbiome profiles differ between patients:

1. with and without symptomatic improvement of CIPN.
2. receiving rectal ozone therapy and those receiving placebo.

Secondary Objectives:

To evaluate the relationship between gut microbiome composition and:

1. Health-related quality of life,
2. Anxiety and depression,
3. Biochemical markers of oxidative stress and inflammation.

Main Trial Endpoints.

Changes from baseline at the end of ozone therapy (week 16) in:

* Gut microbiome profile
* Patient-reported numbness and tingling
* Neuropathy severity (QLQ-CIPN20 scale)
* Paresthesia toxicity grade (CTCAE v.5.0)

Secondary Trial Endpoints.

Changes from baseline at the end of ozone therapy (week 16) in:

* Patient-reported quality of life (EQ-5D-5L questionnaire)
* Quality of life (QLQ-C30 questionnaire)
* Anxiety and depression levels (HADS questionnaire)
* Biochemical markers of oxidative stress
* Biochemical markers of inflammation

Trial Design:

This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544).

Trial Population in the OzoParQT trial (NCT06706544):

Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months.

Intervention in the OzoParQT trial (NCT06706544).

All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks:

* Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL
* Control-placebo group: O2 only (0 µg/mL O3)

Study Duration:

Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.

Conditions

• Chemotherapy Induced Peripheral Neuropathy (CIPN)
• Paresthesia
• Numbness
• Tingling

Interventions

DRUG

Ozone therapy

Usual treatment (by their oncologist or hematologist) + Ozone therapy by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.

DRUG

Oxygen (placebo)

Usual treatment (by their oncologist or hematologist) + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.

Sponsors & Collaborators

• Fundacion Canaria Instituto de Investigacion Sanitaria de Canarias

  collaborator OTHER

• Instituto de Salud Carlos III

  collaborator OTHER_GOV

• Council of Gran Canaria

  collaborator OTHER

• CIBER (Infectious diseases)

  collaborator UNKNOWN

• Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna

  collaborator UNKNOWN

• Bernardino Clavo, MD, PhD

  lead OTHER

Principal Investigators

• Bernardino Clavo, MD, PhD · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

• Francisco Rodríguez-Esparragón, BSc, PhD · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

• Jacob Lorenzo-Morales, Prof · Instituto Universitario de Enfermedades Tropicales y Salud Publica de Canarias - Universidad de La Laguna (IUETSPC-ULL)

• Francisco Rodríguez-Esparragón, BSc, PhD · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

• Bernardino Clavo, MD, PhD · Hospital Universitario de Gran Canaria Dr. Negrín, (FIISC), Las Palmas, Spain

Study Design

Allocation

RANDOMIZED

Purpose

SCREENING

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-07

Primary Completion

2029-12-31

Completion

2030-03-31

Countries

• Spain

Study Locations