Neuroprotection of Memantine and Rosuvastatin

Neuroprotective Effect of Memantine and Rosuvastatin Against Oxaliplatin Induced Peripheral Neuropathy in Patients With Colorectal Cancer

Memantine is used to slow the neurotoxicity of Alzheimer disease. Rosuvastatin used as a lipid-lowering agent . Increased bioavailability of endothelial-derived nitric oxide improves endothelium function , increases cerebral blood flow which may all contribute to the neuroprotective effects of rosuvastatin .

The goal of this clinical trial is to prevent oxaliplatin induced peripheral neuropathy in patients with colorectal cancer.The aim of this current study is to assess the neuroprotective effect of memantine and rosuvastatin against oxaliplatin induced peripheral neuropathy.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Nerve Disease
• Intervention / Treatment: Drug: Starch Placebo; Drug: Memantine; Drug: Rosuvastatin 20 Mg Oral Tablet

Detailed Description

Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species and lipid product malondialdehyde expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin Rosuvastatin decreases axonal injury and cortical thickness. Rosuvastatin attenuated the chronic constriction injury induced neuropathic pain and inflammation .Thus, antinociceptive effects of rosuvastatin might be channeled through inhibition of inflammatory biomarkers and antioxidant properties .

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Eman Ayman Elsayed Abdallah a Abdallah, Pharm D; Phone Number: 022+01285941144; Email: aymanemy155@gmail.com
• Study Contact Backup: Name: Eman Ibrahim Abd Elkhader El berry i Lecturer of Clinical Pharmacy, MD

Study Locations

• Egypt
  • Tanta, Egypt
    • Tanta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Age above 18 years old for both gender .
• Adequate baseline hematologic values (absolute neutrophil 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 ˃ 45 mL/min).
• Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).
• Patients with performance status <2 according to Eastern Cooperative Oncology Group (ECOG) score.
• Patients who will be scheduled to receive modified FOLFOX-6 or XELOX regimen.
• Patients with histologically confirmed diagnosis of stage III or stage IV colorectal cancer.

Exclusion criteria:

• Children < 18 years old.
• Prior exposure to neurotoxic chemotherapy (oxaliplatin, cisplatin, vincristine, paclitaxel, or docetaxel, INH).
• Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases, hepatitis C.
• History of known allergy to oxaliplatin or other platinum agents.
• Patients with other inflammatory or stressful conditions.
• Concomitant use of multivitamins (vitamins E, C, A), tricyclic antidepressants, other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin).
• Patients on amantadine , acetazolamide, dextromethorphan, aluminum hydroxide magnesium hydroxide and febuxostat .
• Concurrent active cancer originating from a primary site other than colon or rectum.
• Pregnant and breastfeeding women.
• Sever renal insufficiency (creatinine clearance < 25 ml/ minute) .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Standard group; Patients will receive modified FOLFOX-6 regimen or XELOX regimen The chemotherapy cycles will be received every 14 days for modified FOLFOX-6 regimen or every 21 days for XELOX regimen for 6 months and will be as follows :modified FOLFOX regimen , oxaliplatin 85 mg/m2 intravenous infusion in 500 mL 5% dextrose solution(on days 1 and 15) and leucovorin 400 mg/m2 intravenous infusion in 250 mL 5% dextrose solution both were given over 2 hours at the same time in separate bags using a Y-line access , followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 5 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenous infusion in 500 mL 5% dextrose solution as a 46-hour infusion. XELOX regimen , oxaliplatin 130 mg/m2 intravenous infusion in 500 mL 5% dextrose over 2 hours and capecitabine 850 mg/m2 or 1000 mg/m2 per dose twice daily (total dose 1700 or 2000 per day )from evening of day 1 to morning of day15 plus starch placebo orally	Drug: Starch Placebo; starch placebo oral tablet will be given to patients plus the modified FOLFOX chemotherapy regimen or XELOX chemotherapy regimen
Active Comparator: Intervention group; patients with colorectal cancer will receive modified FOLFOX-6 regimen or XELOX regimen throughout the chemotherapy cycles plus memantine oral tablet 5 mg PO once daily initially; increased by increments of 5 mg/day each week; maintenance target dosage 20 mg/day and rosuvastatin tablet 20 mg orally daily.	Drug: Memantine; memantine 5 mg PO once daily initially; increased by increments of 5 mg/day each week; maintenance target dosage 20 mg/day; Drug: Rosuvastatin 20 Mg Oral Tablet; rosuvastatin 20 mg orally daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome is the percentage of patients with sensory neuropathy grade ≥ 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events for grading of neuropathy from 1 to 5 based on severity.	at base line and every two oxaliplatin cycle (each cycle is 14 days )

Secondary Outcome Measures

Outcome Measure	Time Frame
the changes in serum levels of the Serum neurofilament light chain as a biomarker of neuronal damage, Serum malondialdhyde as a marker of oxidative stress and Serum tumor necrosis factor alpha as a biomarker of inflammation	at base line and after the completion of chemotherapy cycle(6 months)

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Eman Ayman Elsayed Abdallah a Abdallah, Pharm D, Tanta University

Publications and helpful links

General Publications

• Ma G, Liu C, Hashim J, et al. Memantine mitigates oligodendrocyte damage after repetitive mild traumatic brain injury. Neuroscience, 2019;421:152-161.
• Wei G, Gu Z, Gu J, Yu J,et al. Platinum accumulation in oxaliplatin-induced peripheral neuropathy. J Peripher Nerv Syst., 2021;26(1):35-42.
• Zisiadis GA, Alevyzaki A, Nicola E, et al. Memantine increases the dendritic complexity of hippocampal young neurons in the juvenile brain after cranial irradiation. Front Oncol., 2023;13:1202200.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 15, 2026
• First Submitted That Met QC Criteria: March 25, 2026
• First Posted (Actual): March 31, 2026

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Hydrocarbons; Hydrocarbons, Cyclic; Amides; Pyrimidines; Hydrocarbons, Halogenated; Adamantane; Bridged-Ring Compounds; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Amantadine; Rosuvastatin Calcium; Memantine; Tablets
• Other Study ID Numbers: 36264MS461/12/23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes