The Role of Coenzyme Q10 in the Prophylaxis of Oxaliplatin Induced Peripheral Neuropathy in Patients With Colorectal Cancer

Phase 1

Recruiting

• Conditions: Colorectal Cancer
• Interventions: Drug: Oxaliplatin; Drug: Coenzyme Q10; Drug: 5-Fluorouracil (5-FU); Drug: 5-HT3 Antagonist; Drug: Pantoprazole

• Registration Number: NCT06856447
• Lead Sponsor: toqa saad mohammed mohammed

Brief Summary

This study aims to evaluate the possible beneficial role of coenzyme Q10 against oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer.

Detailed Description

Oxaliplatin (OXA), a third-generation platinum-based anticancer drug, has better efficacy and lower toxicity than cisplatin and carboplatin. Currently, OXA combined with 5-FU and leucovorin is the standard adjuvant chemotherapy regimen for colorectal cancer (CRC) and the first-line treatment for metastatic CRCs. The major side effects of OXA include peripheral neurotoxicity, myelosuppression, and diarrhea. These adverse effects may lead to treatment discontinuation and reduced compliance among CRC patients. Specifically, oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity associated with OXA.

The mechanisms involved in OIPN include functional abnormalities in voltage-gated K+ channels, with increased expression of pro-excitatory K+ channels such as hyperpolarization-activated channels. Abnormalities in Na+ currents have been detected in 78% of patients who later develop chronic OXA-induced neuropathy (Krishnan et al., 2005). Dysregulation of Ca2+ homeostasis has also been suggested as a key factor in OXA-associated nerve damage. In vivo studies indicate that oxaliplatin-induced cold allodynia enhances the sensitivity and expression of transient receptor potential A1 (TRPA1) and transient receptor potential cation channel subfamily M member 8 (TRPM8).

Several studies suggest a relationship between OXA-induced neuropathy and oxidative stress. Additional potential contributors to neuropathic pain include T-cells (Th17 and Th1) and inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α). Clinical studies have demonstrated that elevated IL-6 levels correlate with painful chemotherapy-induced neuropathy, and patients receiving IL-6 neutralizing antibodies as part of their therapy report reduced neuropathic pain compared to those not receiving these antibodies.

Coenzyme Q10 (CoQ10) is an oil-soluble, vitamin-like substance primarily present in mitochondria. It possesses anti-inflammatory and antioxidant properties and has demonstrated neuroprotective effects in animal models of neurodegeneration by stimulating cell growth and inhibiting cell death. CoQ10 has been shown to protect against cisplatin-induced neurotoxicity in a rat model and to reduce paclitaxel-induced peripheral neuropathy in rodents. Additionally, CoQ10 exhibited a protective effect against vincristine-induced peripheral neuropathy in rats (Elshamy et al., 2022). The neuroprotective effects of CoQ10 have been attributed to its ability to mitigate oxidative stress and inflammation, evidenced by significant reductions in malondialdehyde (MDA), 8-hydroxyguanosine (8-OHdG), TNF-α, IL-1β, and nuclear factor kappa-B. CoQ10 has also been reported to lower serum neurofilament-light chain (NF-L), a recognized biomarker for multiple neurodegenerative diseases.

In diabetic patients with peripheral neuropathy, antioxidant and anti-inflammatory supplementation with CoQ10 has shown potential benefits. A study reported that administration of CoQ10 at a dose of 200 mg/day for 12 weeks in neuropathic diabetic patients improved total antioxidant capacity (TAC) and reduced high-sensitivity C-reactive protein (hsCRP).

To the best of the investigators' knowledge, no clinical trials have been conducted to evaluate CoQ10 as a prophylactic therapy against chemotherapy-induced neuropathy. This study aims to assess its potential role in preventing oxaliplatin-induced peripheral neuropathy.

Study Timeline

• Study Start: 2024-06-01
• Study First Submitted: 2024-06-03
• Status Verified: 2025-02
• Study First Submitted QC: 2025-02-26
• Last Update Submitted: 2025-02-26
• Study First Posted: 2025-03-04
• Last Update Posted: 2025-03-04
• Primary Completion: 2025-05-20
• Study Completion: 2026-01-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Patients with histologically confirmed diagnosis of Stage III colorectal cancer.
• Patients who will be scheduled to receive modified FOLFOX-6.
• Patients with no contraindication to chemotherapy.
• Males and females aged ≥ 18 years old.
• 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
• Patients with adequate liver function (serum bilirubin < 1.2 mg/dl).
• Patients with performance status 0-1 according to Eastern Cooperative Oncology Group (ECOG) score.
• Patients who may receive medications to counteract chemotherapy induced neuropathic pain (gabapentin, lamotrigine, carbamazepine, etc....).

Exclusion Criteria

• Exclusion criteria

  • Patients with prior exposure to neurotoxic agents (Cisplatin, vincristine, paclitaxel, docetaxol, foscarnet, INH, etc..) in the last 6 months.
  • Patients with evidence of metastasis at the initial assessment.
  • Concomitant use of antioxidant vitamins (vitamin A, C, E),
  • Preexisting peripheral neuropathy resulting from other causes such as diabetes and brain disorders, hypothyroidism, autoimmune diseases, hepatitis C.
  • Patients with diabetes.
  • Patients with inflammatory diseases (ulcerative colitis, rheumatoid arthritis).
  • Patients with stressful conditions as smoking, COPD, ....
  • Patients with active liver disease (cirrhosis, fatty liver, hepatitis C, etc..).
  • Patients with myopathy
  • Patients with renal impairment, including those with end-stage renal disease and those receiving dialysis.
  • Pregnant and breast feeding women.
  • Concurrent use of diltiazem, metoprolol, enalapril, nitroglycerin, warfarin, clopidigrel, aspirin, statins, fibrates, tricyclic antidepressant medications,

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Oxaliplatin	Patients in the control group will receive 12 cycles of the modified FOLFOX-6 regimen, which consists of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin, administered every two weeks. Supportive care includes an intravenous 5-HT3 antagonist for nausea prevention and pantoprazole to prevent gastric irritation.
Control group	5-Fluorouracil (5-FU)	Patients in the control group will receive 12 cycles of the modified FOLFOX-6 regimen, which consists of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin, administered every two weeks. Supportive care includes an intravenous 5-HT3 antagonist for nausea prevention and pantoprazole to prevent gastric irritation.
Control group	5-HT3 Antagonist	Patients in the control group will receive 12 cycles of the modified FOLFOX-6 regimen, which consists of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin, administered every two weeks. Supportive care includes an intravenous 5-HT3 antagonist for nausea prevention and pantoprazole to prevent gastric irritation.
Control group	Pantoprazole	Patients in the control group will receive 12 cycles of the modified FOLFOX-6 regimen, which consists of oxaliplatin, 5-fluorouracil (5-FU), and leucovorin, administered every two weeks. Supportive care includes an intravenous 5-HT3 antagonist for nausea prevention and pantoprazole to prevent gastric irritation.
Experimental	Coenzyme Q10	Patients in the experimental group will receive 12 cycles of the modified FOLFOX-6 regimen with the same supportive medications as the control group. Additionally, they will receive Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle.
Experimental	Oxaliplatin	Patients in the experimental group will receive 12 cycles of the modified FOLFOX-6 regimen with the same supportive medications as the control group. Additionally, they will receive Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle.
Experimental	5-Fluorouracil (5-FU)	Patients in the experimental group will receive 12 cycles of the modified FOLFOX-6 regimen with the same supportive medications as the control group. Additionally, they will receive Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle.
Experimental	5-HT3 Antagonist	Patients in the experimental group will receive 12 cycles of the modified FOLFOX-6 regimen with the same supportive medications as the control group. Additionally, they will receive Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle.
Experimental	Pantoprazole	Patients in the experimental group will receive 12 cycles of the modified FOLFOX-6 regimen with the same supportive medications as the control group. Additionally, they will receive Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle.

Primary Outcome Measures

Name	Time	Method
Tumor necrosis factor-alpha (TNF-α)	Between 8:30 AM and 10:30 AM after overnight fasting. Blood samples will be collected into a plain test tube and centrifuged at 3,000 revolutions per minute (RPM) for 10 minutes.	Tumour Necrosis Factor alpha (TNF alpha), is an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signalling events within cells, leading to necrosis or apoptosis.

Secondary Outcome Measures

Name	Time	Method
Neurofilament-light chain (NF-L).	Between 8:30 AM and 10:30 AM after overnight fasting. Blood samples will be collected into a plain test tube and centrifuged at 3,000 revolutions per minute (RPM) for 10 minutes.	eurofilament-light chain (Nf-L) is a reliable biomarker in the context of neurodegenerative diseases (NDD) and traumatic brain injuries (TBI).

Trial Locations

Locations (1)

Ain-Shams University Hospital; 🇪🇬 Cairo, Egypt