Peripheral Nerve Disease
Conditions
Brief summary
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.
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 .
Interventions
DRUGStarch Placebo
starch placebo oral tablet will be given to patients plus the modified FOLFOX chemotherapy regimen or XELOX chemotherapy regimen
DRUGMemantine
memantine 5 mg PO once daily initially; increased by increments of 5 mg/day each week; maintenance target dosage 20 mg/day
rosuvastatin 20 mg orally daily.
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Intervention model description
patients with colorectal cancer will receive the standard chemotherapy regimen therapy plus memantine 5 mg PO once daily initially; increased by increments of 5 mg/day each week; maintenance target dosage 20 mg/day and rosuvastatin 20 mg orally daily.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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) .
Design outcomes
Primary
| 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
| 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) |
Countries
Egypt
Contacts
CONTACTEman Ayman Elsayed Abdallah a Abdallah, Pharm D
CONTACTEman Ibrahim Abd Elkhader El berry i Lecturer of Clinical Pharmacy, MD
PRINCIPAL_INVESTIGATOREman Ayman Elsayed Abdallah a Abdallah, Pharm D
Tanta University
Outcome results
None listed