Evaluation of the Gut Microbiome Profiles in Patients With Chemotherapy-induced Peripheral Neuropathy Treated in the Randomized Clinical Trial With Ozone OzoParQT (NCT06706544).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Change from baseline in gut microbiome profile, at the end of ozone therapy.
研究概览
简要总结
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:
- with and without symptomatic improvement of CIPN.
- receiving rectal ozone therapy and those receiving placebo.
Secondary Objectives:
To evaluate the relationship between gut microbiome composition and:
- Health-related quality of life,
- Anxiety and depression,
- 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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
- the oncologists/hematologists who treat and follow the patient regularly,
- researchers who carry out biochemical determinations or functional tests,
- researchers who carry out the gut microbiome analysis,
- statisticians
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •0. Patients who agree to participate in the randomized clinical trial OzoParQT, and who also agree to participate in this study of gut microbiota by providing stool samples.
- •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 is 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 14 days before the first ozone therapy session up to 14 days after the last one.
- •8. To sign and date the specific informed consent of both studies (OzoParQT and OzoParQTmicrob)
排除标准
- •1. Age < 18 years.
- •2. A woman who is lactating, pregnant, suspected of being pregnant, or a woman of childbearing potential who 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
研究组 & 干预措施
Ozone Group
Drug: Ozone (O3/O2). Treatment: Usual treatment + Ozone therapy by rectal insufflation. O3/O2 concentration progressively increased from 10 to 30 μg/ml; 40 sessions in 16 weeks.
干预措施: Ozone therapy (Drug)
Oxygen Group (Placebo)
Drug: Oxygen (O2). Treatment: Usual treatment + Oxygen by rectal insufflation. O3/O2 concentration = 0 μg/ml (only O2); 40 sessions in 16 weeks.
干预措施: Oxygen (placebo) (Drug)
结局指标
主要结局
Change from baseline in gut microbiome profile, at the end of ozone therapy.
时间窗: 16 weeks.
Analysis of gut microbiome profile at the end of ozone therapy regarding the basal profile.
Change from baseline in "numbness and tingling" self-perceived by patients at the end of ozone treatment.
时间窗: 16 weeks.
Self-reported evaluation of the percentage of "numbness and/or tingling" regarding the basal level. From 100% (basal level, 0% improvement) to 0% (no numbness and tingling, 100% improvement).
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment.
时间窗: 16 weeks.
Changes from baseline in the degree of neuropathy according to the QLQ-CIPN20 scale at the end of ozone treatment (from the European Organization for Research \& Treatment in Cancer (EORTC)). It is evaluated through 20 items grouped into 3 dimensions: sensory, 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 score from 0 to 100, with 0 being the best possible state and 100 being the worst.
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.
时间窗: 16 weeks.
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). Range from: Grade = (asymptomatic or mild symptoms) to Grade 3 (severe symptoms, limiting self-care activities in daily life).
次要结局
- Change from baseline in "Quality of Life" (using the EQ-5D-5L questionnaire) self-perceived by patients at the end of ozone treatment.(16 weeks.)
- Changes from baseline in the "Quality of Life" according to the QLQ-C30 questionnaire at the end of ozone treatment.(16 weeks.)
- Changes from baseline in biochemical parameters of oxidative stress at the end of ozone treatment.(16 weeks.)
- Changes from baseline in levels of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS), at the end of ozone treatment.(16 weeks.)
- Changes from baseline in biochemical parameters of inflammation at the end of ozone treatment.(16 weeks.)
研究者
Bernardino Clavo, MD, PhD
Bernardino Clavo, MD, PhD, Dr. Negrin University Hospital
Hospital Universitario de Gran Canaria Doctor Negrín