Neuroprotection of Memantine and Rosuvastatin

Tanta University

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Peripheral Nerve Disease

Treatments: Drug: Memantine; Drug: Rosuvastatin 20 Mg Oral Tablet; Drug: Starch Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07504198

36264MS461/12/23

Details and patient eligibility

About

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.

Full 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 .

Enrollment: 46 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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) .

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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46 participants in 2 patient groups, including a placebo group

Standard group

Placebo Comparator group

Description:

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

Treatment:

Drug: Starch Placebo

Intervention group

Active Comparator group

Description:

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.

Treatment:

Drug: Rosuvastatin 20 Mg Oral Tablet

Drug: Memantine