Protective Effect of N-acetylcysteine on Oxaliplatin-Induced Neuropathy in Colorectal Cancer

NCT07391163 | Completed

• 1 other identifier: 36264MS490/1/24
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer; Oxaliplatin; Peripheral Neuropathy; N-Acetylcysteine; Oxaliplatin Induced Peripheral Neuropathy

Outcome Measures

Primary Outcomes (3)

• NCI-CTCAE, Version 5, 2017

  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.

  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.

• FACT/GOG-Ntx-12

  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.

  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.

• BPI-SF

  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.

  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.

Secondary Outcomes (3)

• 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.

Study Arms (2)

NAC Group

EXPERIMENTAL

Patients receive modified FOLFOX-6 chemotherapy plus oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.

Drug: N-Acetyl Cysteine; Drug: Modified FOLFOX-6 regimen

Placebo Group

PLACEBO COMPARATOR

Patients receive modified FOLFOX-6 chemotherapy plus oral placebo tablets administered 1 hour before oxaliplatin throughout chemotherapy cycles.

Drug: Placebo; Drug: Modified FOLFOX-6 regimen

Interventions

Placebo DRUG

Oral placebo tablets identical in appearance to N-acetyl cysteine, administered 1 hour before oxaliplatin throughout chemotherapy cycles.

Placebo Group

N-Acetyl Cysteine DRUG

Oral N-acetyl cysteine 1200 mg administered 1 hour before oxaliplatin throughout chemotherapy cycles.

NAC Group

Modified FOLFOX-6 regimen DRUG

Oxaliplatin 85 mg/m² IV, leucovorin 400 mg/m² IV, followed by 5-fluorouracil bolus and continuous infusion every 2 weeks.

NAC Group; Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-6.
• Patients with no contraindication to chemotherapy.
• Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5
• /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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta University - Faculty of Medicine ,oncology department, Tanta university hospital.

Tanta, Egypt

Location

Related Publications (4)

• Starobova H, Vetter I. Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy. Front Mol Neurosci. 2017 May 31;10:174. doi: 10.3389/fnmol.2017.00174. eCollection 2017.

  PMID: 28620280 BACKGROUND

• Tardiolo G, Bramanti P, Mazzon E. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules. 2018 Dec 13;23(12):3305. doi: 10.3390/molecules23123305.

  PMID: 30551603 BACKGROUND

• Baidoun F, Elshiwy K, Elkeraie Y, Merjaneh Z, Khoudari G, Sarmini MT, Gad M, Al-Husseini M, Saad A. Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes. Curr Drug Targets. 2021;22(9):998-1009. doi: 10.2174/1389450121999201117115717.

  PMID: 33208072 BACKGROUND

• Tardiolo G, Bramanti P, Mazzon E. Overview on oxidative stress and inflammation induced by chemotherapy. International Journal of Molecular Sciences. 2019;20(15):3771.

  BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Peripheral Nervous System Diseases

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Nehal Mohamed Elmashad, Professor

  Department of Clinical Oncology ,Tanta University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pharmacist & Clinical Researcher

Model Details: This is a Randomized, placebo-controlled, parallel-group study. Forty-six patients with stage III colorectal cancer and high-risk stage II will be randomly assigned in a 1:1 ratio to one of two arms: Arm 1 (Placebo Group, n=23): Patients will receive 4-6 cycles of modified FOLFOX-6 chemotherapy (Oxaliplatin, Leucovorin, and 5-Fluorouracil) plus oral placebo tablets throughout the chemotherapy cycles. Arm 2 (Drug / Experimental Group, n=23): Patients will receive the same chemotherapy regimen in addition to oral N-Acetyl Cysteine 1200 mg administered 1 hour before Oxaliplatin infusion throughout chemotherapy cycles. Patients will be recruited from the Oncology Department, Tanta University Hospital, Egypt. Randomization will be done using a sealed envelope method. Standard antiemetic and gastric prophylaxis therapy (IV 5-HT3

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: February 5, 2026
• Study Start: January 1, 2024
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: February 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)