The Possible Protective Role of N-Acetylcysteine Against Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- NCI-CTCAE, Version 5, 2017
研究概览
简要总结
This study investigates the possible protective role of N-Acetylcysteine against oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. The trial aims to evaluate whether N-Acetylcysteine can reduce the incidence and severity of neuropathy during chemotherapy.
详细描述
Oxaliplatin, a common chemotherapeutic agent for colorectal cancer, often induces peripheral neuropathy, which can significantly affect patients' quality of life and limit treatment effectiveness. The neuropathy is partly caused by nerve inflammation and oxidative stress.
N-Acetylcysteine (NAC), an antioxidant, has been suggested to protect neurons from oxidative damage and reduce inflammation.
This interventional, randomized, parallel-assignment study will enroll colorectal cancer patients receiving oxaliplatin-based chemotherapy. Participants will be assigned to either receive N-Acetylcysteine alongside chemotherapy or chemotherapy alone. Primary outcomes include the incidence and severity of peripheral neuropathy measured at predefined intervals during treatment.
Secondary outcomes include biochemical markers of nerve inflammation and oxidative stress, including:
- Neurotensin (marker of nerve inflammation)
- Interleukin-6 (marker of systemic inflammation)
- Total Antioxidant Capacity (marker of oxidative stress)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged ≥ 18 years old.
- •Patients with histologically confirmed diagnosis of Stage III colorectal cancer and high risk Stage II.
- •Patients who will be scheduled to receive modified FOLFOX-
- •Patients with no contraindication to chemotherapy.
- •Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5
- •109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
- •Patients with adequate renal function (serum creatinine < 1.5 mg/dl or creatinine clearance (ClCr) ˃ 45 mL/min).
- •Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).
- •Patients with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG) score.
排除标准
- •Children < 18 years old.
- •Prior exposure to chemotherapy.
- •Patients with diabetes and other conditions that predispose to neuropathy.
- •History of known allergy to oxaliplatin or other platinum agents.
- •Concomitant use of any drug has anti-oxidant activity or neuroprotective agent.
- •Patients take any medication that increase acetyle choline either central or peripheral.
- •Patient was any cardiac disease.
- •Pregnant and breastfeeding women.
研究组 & 干预措施
NAC Group
Patients receive modified FOLFOX-6 chemotherapy plus oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.
干预措施: N-Acetyl Cysteine (Drug)
NAC Group
Patients receive modified FOLFOX-6 chemotherapy plus oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.
干预措施: Modified FOLFOX-6 regimen (Drug)
Placebo Group
Patients receive modified FOLFOX-6 chemotherapy plus oral placebo tablets administered 1 hour before oxaliplatin throughout chemotherapy cycles.
干预措施: Placebo (Drug)
Placebo Group
Patients receive modified FOLFOX-6 chemotherapy plus oral placebo tablets administered 1 hour before oxaliplatin throughout chemotherapy cycles.
干预措施: Modified FOLFOX-6 regimen (Drug)
结局指标
主要结局
NCI-CTCAE, Version 5, 2017
时间窗: Adverse events will be assessed using NCI-CTCAE v5.0 at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.
The CTCAE is an international classification system used to assess and describe adverse events resulting from medical treatments, especially in cancer therapy, chemotherapy, and radiation therapy. It provides standard criteria to grade the severity of each adverse event on a scale from 1 to 5: Grade 1 (Mild): Mild symptoms, no intervention needed. Grade 2 (Moderate): Symptoms require minimal intervention or slightly affect daily activities. Grade 3 (Severe): Symptoms significantly impact daily activities or require medical intervention. Grade 4 (Life-threatening): Life-threatening symptoms requiring urgent intervention. Grade 5 (Death): Death due to the adverse event.
FACT/GOG-Ntx-12
时间窗: Neurotoxicity-related adverse events will be assessed using the FACT/GOG-Ntx-12 at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.
The FACT/GOG-Ntx-12 is a patient-reported outcome measure designed to assess chemotherapy-induced neurotoxicity, particularly from drugs such as platinum agents or taxanes. It consists of 12 items evaluating peripheral neuropathy symptoms, including numbness, tingling, pain, weakness in hands or feet, and difficulty with walking or handling objects. Each item is scored on a 0-4 scale (0 = not at all, 4 = very much), providing a total score reflecting the severity of neurotoxicity. It is primarily used to monitor the impact of chemotherapy on neurological function and related quality of life.
BPI-SF
时间窗: Pain severity and interference will be assessed using the BPI-SF at baseline (Day 1, prior to Cycle 1) and after Cycle 2 (Day 15) and after Cycle 4 (Day 29). Each chemotherapy cycle lasts 14 days.
The BPI-SF (Brief Pain Inventory - Short Form) is a patient-reported questionnaire used to assess pain severity and its impact on daily functioning. It includes questions about the intensity of pain (e.g., worst, least, average, and current pain) and how pain interferes with activities such as walking, work, mood, sleep, and relationships. Each item is rated on a 0-10 numeric scale (0 = no pain / no interference, 10 = worst imaginable pain / complete interference), allowing calculation of overall pain severity and interference scores. It is widely used in cancer patients and other chronic pain conditions to monitor pain and response to treatment.
次要结局
- Serum IL-6 as a marker of inflammation(IL-6 will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.)
- Serum total anti-oxidant capacity (TAC) as a biomarker of oxidative stress(TAC will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.)
- Serum neurotensin as a biomarker for neuropathy(NT will be measured at pre-oxaliplatin infusion (baseline) and after infusion completion (post-dose) on Day 1 of Cycle 1 in both study arms. NAC is administered orally 1 hour before baseline sample in the intervention arm. Each FOLFOX cycle is 14 days.)
研究者
Zeyad Khairy Hegazy
Pharmacist & Clinical Researcher
Tanta University