Clinical trial NCT06856447: The Role of Coenzyme Q10 in the Prophylaxis of Oxaliplatin Induced Peripheral Neuropathy in Patients With Colorectal Cancer
Official title: The Role of Coenzyme Q10 in the Prophylaxis of Oxaliplatin Induced Peripheral Neuropathy in Patients With Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Keywords: Oxaliplatin-induced neuropathy
Coenzyme Q10
Neuroprotection in cancer
Chemotherapy-induced neuropathy
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2025-03-04
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Tumor necrosis factor-alpha (TNF-α)
timeFrame: 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.
Secondary outcomes:
measure: Neurofilament-light chain (NF-L).
timeFrame: 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.
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain-Shams University Hospital
Study officials:
affiliation: Associate Professor of Clinical Oncology Faculty of Medicine - Ain-Shams University
name: Mohamed Reda Kelany, dr
role: STUDY_DIRECTOR
affiliation: Lecturer of Clinical Pharmacy Faculty of Pharmacy - Tanta University
name: Eman Ibrahim Abd Elkader Elberri
role: STUDY_DIRECTOR
References:
citation: Kidwell KM, Yothers G, Ganz PA, Land SR, Ko CY, Cecchini RS, Kopec JA, Wolmark N. Long-term neurotoxicity effects of oxaliplatin added to fluorouracil and leucovorin as adjuvant therapy for colon cancer: results from National Surgical Adjuvant Breast and Bowel Project trials C-07 and LTS-01. Cancer. 2012 Nov 15;118(22):5614-22. doi: 10.1002/cncr.27593. Epub 2012 May 8.
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