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

NCT06856447 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Prophylaxis of neuropathy
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer

Keywords

Oxaliplatin-induced neuropathy; Coenzyme Q10; Neuroprotection in cancer; Chemotherapy-induced neuropathy

Outcome Measures

Primary Outcomes (1)

• Tumor necrosis factor-alpha (TNF-α)

  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.

  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 (1)

• 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.

Study Arms (2)

Control group

PLACEBO COMPARATOR

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.

Drug: Oxaliplatin; Drug: 5-Fluorouracil (5-FU); Drug: 5-HT3 Antagonist; Drug: Pantoprazole

Experimental

EXPERIMENTAL

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.

Drug: Coenzyme Q10; Drug: Oxaliplatin; Drug: 5-Fluorouracil (5-FU); Drug: 5-HT3 Antagonist; Drug: Pantoprazole

Interventions

Coenzyme Q10 DRUG

100 mg once daily starting after the first chemotherapy cycle. Patients will receive 12 cycles of the modified FOLFOX-6 regimen with Coenzyme Q10 (100 mg once daily in the morning), starting after the first chemotherapy cycle and continuing until the end of the 12th cycle. Based on McRae (2023), 200 mg/day for 12 weeks reduced TNF-α and IL-6; thus, 100 mg/day for 6 months was selected (one cycle every 2 weeks = 24 weeks). Supportive care: Includes a 5-HT3 antagonist for nausea prevention and pantoprazole to prevent gastric irritation. Intervention Details: Oxaliplatin: Part of the FOLFOX-6 regimen. 5-Fluorouracil (5-FU): Part of the FOLFOX-6 regimen. Leucovorin: Part of the FOLFOX-6 regimen. 5-HT3 Antagonist: Used for nausea prevention. Pantoprazole: Used to prevent gastric irritation.

Also known as: Coenzyme Q10 Forte

Experimental

Oxaliplatin DRUG

Part of the modified FOLFOX-6 chemotherapy regimen

Control group; Experimental

5-Fluorouracil (5-FU) DRUG

Part of the modified FOLFOX-6 chemotherapy regimen.

Control group; Experimental

5-HT3 Antagonist DRUG

Used for nausea prevention during chemotherapy.

Control group; Experimental

Pantoprazole DRUG

Used to prevent gastric irritation during chemotherapy

Control group; Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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….).

You may not qualify if:

• 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,

Sponsors & Collaborators

• toqa saad mohammed mohammed: lead

Study Sites (1)

Ain-Shams University Hospital

Cairo, Egypt

RECRUITING

Related Publications (9)

• 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.

  PMID: 22569841 BACKGROUND

• Krishnan AV, Goldstein D, Friedlander M, Kiernan MC. Oxaliplatin-induced neurotoxicity and the development of neuropathy. Muscle Nerve. 2005 Jul;32(1):51-60. doi: 10.1002/mus.20340.

  PMID: 15880395 BACKGROUND

• Marmiroli P, Riva B, Pozzi E, Ballarini E, Lim D, Chiorazzi A, Meregalli C, Distasi C, Renn CL, Semperboni S, Morosi L, Ruffinatti FA, Zucchetti M, Dorsey SG, Cavaletti G, Genazzani A, Carozzi VA. Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights. PLoS One. 2017 Oct 11;12(10):e0186250. doi: 10.1371/journal.pone.0186250. eCollection 2017.

  PMID: 29020118 BACKGROUND

• McRae MP. Coenzyme Q10 Supplementation in Reducing Inflammation: An Umbrella Review. J Chiropr Med. 2023 Jun;22(2):131-137. doi: 10.1016/j.jcm.2022.07.001. Epub 2022 Aug 31.

  PMID: 37346240 BACKGROUND

• Nassini R, Gees M, Harrison S, De Siena G, Materazzi S, Moretto N, Failli P, Preti D, Marchetti N, Cavazzini A, Mancini F, Pedretti P, Nilius B, Patacchini R, Geppetti P. Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain. 2011 Jul;152(7):1621-1631. doi: 10.1016/j.pain.2011.02.051. Epub 2011 Apr 9.

  PMID: 21481532 BACKGROUND

• Nielsen DL, Palshof JA, Larsen FO, Jensen BV, Pfeiffer P. A systematic review of salvage therapy to patients with metastatic colorectal cancer previously treated with fluorouracil, oxaliplatin and irinotecan +/- targeted therapy. Cancer Treat Rev. 2014 Jul;40(6):701-15. doi: 10.1016/j.ctrv.2014.02.006. Epub 2014 Feb 28.

  PMID: 24731471 BACKGROUND

• Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014 Dec;155(12):2461-2470. doi: 10.1016/j.pain.2014.09.020. Epub 2014 Sep 23.

  PMID: 25261162 BACKGROUND

• Sommer C, Kress M. Recent findings on how proinflammatory cytokines cause pain: peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004 May 6;361(1-3):184-7. doi: 10.1016/j.neulet.2003.12.007.

  PMID: 15135924 BACKGROUND

• Tan G, Jensen MP, Thornby JI, Shanti BF. Validation of the Brief Pain Inventory for chronic nonmalignant pain. J Pain. 2004 Mar;5(2):133-7. doi: 10.1016/j.jpain.2003.12.005.

  PMID: 15042521 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

coenzyme Q10; Oxaliplatin; Fluorouracil; Serotonin 5-HT3 Receptor Antagonists; Pantoprazole

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mohamed Reda Kelany, dr

  Associate Professor of Clinical Oncology Faculty of Medicine - Ain-Shams University

  STUDY DIRECTOR

• Eman Ibrahim Abd Elkader Elberri

  Lecturer of Clinical Pharmacy Faculty of Pharmacy - Tanta University

  STUDY DIRECTOR

Central Study Contacts

toqa saad mohammed mohammed, master

CONTACT

01096266316; toqasaad45@gmail.com

Tarek pro Mostafa mohamed, pro

CONTACT

01154594035; Tarek77@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Master's Researcher in Clinical Pharmacy, Tanta University

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: March 4, 2025
• Study Start: June 1, 2024
• Primary Completion: May 20, 2025
• Study Completion: January 10, 2026
• Last Updated: March 4, 2025

Record last verified: 2025-02

Locations

EG (1)