Trimetazidine Efficacy in Attenuating Paclitaxel-Induced Peripheral Neuropathy

Phase 1

Completed

• Conditions: Peripheral Neuropathy Due to Chemotherapy
• Interventions: Drug: Placebo; Drug: Trimetazidine

• Registration Number: NCT06459193
• Lead Sponsor: Minia University

Brief Summary

This proof-of-concept study evaluated the effect of Trimetazidine on the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer.

Detailed Description

Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of many commonly used chemotherapeutic agents that greatly affect patient quality of life. Paclitaxel (PTX), one of the main neurotoxic classes of anticancer drugs, is used to treat several types of solid tumors, including breast cancer. Development of PTX-induced peripheral neuropathy (PIPN) during cancer treatment requires dose reduction limiting its clinical benefits.

The only currently recognized prophylactic measure for chemotherapy-induced peripheral neuropathy (CIPN) is monitoring for pre-existing neuropathies and then the early detection of clinical symptoms of neuropathy in subjects undergoing neurotoxic chemotherapy treatment.

Preclinical data has shown that the neuroprotective effect of trimetazidine (TMZ) can attenuate PIPN.

TMZ has preclinical evidence about its preventive capacity against peripheral neuropathy. Which represents a possible prophylactic strategy for attenuating PIPN. TMZ is commercially available in various preparations that are relatively affordable and well-tolerated, making it a valid candidate for clinical evaluation.

Study Timeline

• Study First Submitted: 2024-06-10
• Study First Submitted QC: 2024-06-10
• Study First Posted: 2024-06-14
• Study Start: 2024-06-23
• Primary Completion: 2025-01-28
• Status Verified: 2025-03
• Study Completion: 2025-03-27
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

• Breast cancer patients who will receive paclitaxel.
• Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.
• Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count≥100,000/mm3), liver function (serum total bilirubin <1.5 mg/dl), renal function (creatinine < 1.5 mg/dl).

Exclusion Criteria

• Patients with signs and symptoms of clinical neuropathy at baseline.
• Patients with diabetes mellitus, alcoholic disease, heart failure, pregnant or lactating women.
• Patients receiving vitamin/ supplementation drugs that interfere with the study intervention.
• Patients with contraindications to trimetazidine including Parkinson's disease, Parkinsonian symptoms, tremors, restless leg syndrome, and other related movement disorders.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	Placebo once daily for the treatment period
Intervention	Trimetazidine	Trimetazidine Tablet 35 mg once daily for the treatment period

Primary Outcome Measures

Name	Time	Method
Incidence of chemotherapy induced-peripheral neuropathy using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria	weekly for up to 8 weeks	Number of patients reported neuropathy from paclitaxel. a 1 to 5 graded scale; where grade (1) is the minimum value and grade (5) is the maximum value, a greater grades mean greater symptomatic burden.
Patient's Quality of Life	at baseline, at the end of 4 weeks and at the end of 8 weeks	measures the quality of life using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity FACT/GOG-NTX (Version 4) questionnaire.; A total score ranging from 0 (minimum value) to 44 (maximum value), where lower scores mean greater symptomatic burden.

Secondary Outcome Measures

Name	Time	Method
Changes in serum levels of biomarker namely nerve growth factor (NGF).	at baseline and at end of 8 weeks	measuring serum level of nerve growth factor using enzyme-linked immunoassay (ELISA) Kit.
Adverse effects of using trimetazidine in preventing Paclitaxel Induced Peripheral Neuropathy.	at baseline and weekly up to 8 week	any adverse/ side effect will be evaluated.
Severity of chemotherapy induced-peripheral neuropathy.	at baseline, at the end of 4 weeks and at the end of 8 weeks	The severity of paclitaxel-induced peripheral neuropathy using VAS visual analogue scale.; a 10-cm line that represents a continuum between "no pain" and "worst pain."

Trial Locations

Locations (1)

Minia Oncology Center; 🇪🇬 Minya, Egypt