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

Registry record from ClinicalTrials.gov (NCT06799351). This is a study registration, not published results. Lead sponsor: Bernardino Clavo, MD, PhD. Recruitment status: RECRUITING. Phase: PHASE2, PHASE3. Study type: INTERVENTIONAL. Enrollment: 42 participants (ESTIMATED). Conditions: Chemotherapy Induced Peripheral Neuropathy (CIPN), Paresthesia, Numbness, Tingling. Interventions: DRUG: Ozone therapy; DRUG: Oxygen (placebo). Primary outcome measures: Change from baseline in gut microbiome profile, at the end of ozone therapy. , 16 weeks.; Change from baseline in "numbness and tingling" self-perceived by patients at the end of ozone treatment. , 16 weeks.; Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment. , 16 weeks.; Changes from baseline in the Grade of toxicity of parestesias (numbness, tingling) according to the CTCAE v.5.0. scale at the end of ozone treatment. , 16 weeks.. Brief 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.