Nephrotoxicity
Conditions
Keywords
Cisplatin, Vitamin C, CoQ10, cancer, nephrotoxicity, KIM-1
Brief summary
Cisplatin is a widely used chemotherapy drug for many solid tumors (e.g., lung, bladder, ovarian, head and neck cancers). Despite its efficacy, its clinical use is limited by severe side effects, mainly nephrotoxicity, which occurs in \ 30% of patients after treatment. Once inside cells, cisplatin undergoes activation, leading to DNA and mitochondrial damage, oxidative stress, inflammation, apoptosis, and eventual acute kidney injury (AKI) or chronic kidney disease (CKD). Vitamin C (ascorbic acid) is a water-soluble antioxidant with broad protective roles, including free radical scavenging, DNA and protein protection, and glutathione restoration. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant involved in mitochondrial energy production and regeneration of other antioxidants (vitamins C & E). Both antioxidants are generally safe at studied doses, with only mild gastrointestinal side effects reported. Therefore, evaluating their role in preventing cisplatin-induced nephrotoxicity in cancer patients is clinically valuable. Aim of the study : This study aims to evaluate the protective effects of (Vitamin C and Coenzyme q10) against cisplatin-induced nephrotoxicity in chemotherapy-naïve cancer patients.
Detailed description
Cisplatin is a widely used chemotherapeutic agent in the treatment of several solid tumors; however, its clinical use is limited by nephrotoxicity, which occurs in a significant proportion of patients. Cisplatin-induced renal injury is primarily associated with oxidative stress, inflammation, and mitochondrial dysfunction leading to tubular cell damage. Vitamin C is a potent antioxidant that scavenges reactive oxygen species and may reduce oxidative damage in renal tissues. Coenzyme Q10 is an essential component of the mitochondrial electron transport chain and has strong antioxidant properties that may help protect renal cells from oxidative stress and mitochondrial injury. This randomized controlled trial aims to evaluate the potential renoprotective effects of Vitamin C and Coenzyme Q10 in chemotherapy-naïve cancer patients receiving cisplatin-based chemotherapy. Participants will be randomly allocated to receive antioxidant supplementation along with standard chemotherapy or standard therapy alone. Renal function will be monitored during treatment to assess the protective effects of these interventions. The findings of this study may provide evidence for efficacy to reduce cisplatin-induced nephrotoxicity and improve clinical outcomes for cancer patients undergoing chemotherapy.
Interventions
DRUGVitamin C
Vitamin C 500 mg administered orally
DRUGCoenzyme Q 10
30 mg administered orally
Sponsors
Ain Shams University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Standard of care will be given to all patients. Which includes: The chemotherapy regimen consists of ; cisplatin+gemcitabine. day 1: gemcitabine+ cisplatin: 75 mg/m2 IV , or gemcitabine +fractionated cisplatin: 35 mg /m2 on day 1 and day 8. This regimen will be repeated every 3 weeks for 3 cycles. All patients should receive a hydration protocol based on the chemotherapy protocol. Stratified randomization based on receiving radiotherapy will be done to make sure all groups are balanced. Intervention: Vitamin C orally (500mg) administered orally once daily for 10 days and coQ10 orally (30mg) administered orally once daily for 10 days.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chemotherapy-naïve patients diagnosed with different types of cancer. * Age :adult patients (aged 18-65 years) * Candidates eligible for induction chemotherapy (cisplatin+gemcitabine). Baseline (eGFR) ≥60 ml/min/1.73 m². * Eastern Cooperative Oncology Group (ECOG) performance status \<2. * Hematologic parameters (WBC count ≥ 3,000/mm³ -- Platelet count ≥ 75,000/mm³-- Hb level ≥ 8.0 g/dL) * Alanine aminotransferase (ALT) ≤3×(ULN).
Exclusion criteria
* Prior chemotherapy. * Uncontrolled Diabetes mellitus, active infection, heart failure, liver impairment, gastritis or G-6-P) deficiency. * History of nephrotoxic drugs use over the past 3 months prior to recruitment (e.g., aminoglycosides, amphotericin B, or vancomycin). * Known allergy to any of the study drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the potential protective effects of Vitamin C and Coenzyme Q10 against cisplatin-induced nephrotoxicity in chemotherapy-naïve cancer patients. | 3 cycles (21 days each). | The Incidence and severity of nephrotoxicity is the main outcome as The assessment based on serum creatinine elevation and Graded according to CTCAE version 5.0 Unit of Measure: CTCAE grade |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| KIM-1 biomarker levels | 3 cycles (21 days each). | As an early indicator of acute cisplatin induced kidney injury. |
| Assesment of the quality of life | 3 cycles (21 days each) and it will be measured by the end of the third cycle | Assesment of the quality of life through The European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) questionnaire as it consists of 30 items that assess five functional domains, three symptom domains, a global health status/quality-of-life scale and each item is scored on a 4-point Likert scale:1 for Not at all and 4 for Very much, but the global health status items are scored on a 7-point scale ranging from very poor to excellent. Scores are linearly transformed to a 0-100 scale: Higher functional scores = better functioning / better QoL Higher symptom scores = greater symptom burden |
Countries
Egypt
Contacts
CONTACTGhada S Elseidy, Master
CONTACTRana S Fouad, PHD
PRINCIPAL_INVESTIGATORNagwa A Sabri, PHD
Professor of Clinical Pharmacy-Faculty of Pharmacy-Ain Shams University
Outcome results
None listed