Trimetazidine Efficacy in Attenuating Paclitaxel-Induced Peripheral Neuropathy

Peripheral Neuropathy Due to Chemotherapy Clinical Trial

Official title:

Evaluation of Trimetazidine in Alleviating Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06459193
• Other study ID #: 2301006
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 16, 2024
• Est. completion date: November 30, 2024

Study information

• Verified date: June 2024
• Source: Minia University
• Contact: Asmaa Najm Iqbal Ahmed, Demonstrator
• Phone: +201091965003
• Email: asmaa.najm98[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: November 30, 2024
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Peripheral Nervous System Diseases
• Peripheral Neuropathy Due to Chemotherapy

Intervention

Drug:
• Trimetazidine
Trimetazidine 35 mg tab once daily
• Placebo
Placebo once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Minia University

References & Publications (3)

Hammad ASA, Sayed-Ahmed MM, Abdel Hafez SMN, Ibrahim ARN, Khalifa MMA, El-Daly M. Trimetazidine alleviates paclitaxel-induced peripheral neuropathy through modulation of TLR4/p38/NF-kappaB and klotho protein expression. Chem Biol Interact. 2023 May 1;376:110446. doi: 10.1016/j.cbi.2023.110446. Epub 2023 Mar 9. — View Citation

Haroun EA, Mansour NO, Eltantawy A, Shams MEE. Effect of cilostazol on preventing paclitaxel-induced neuropathy in patients with breast cancer: A randomized controlled trial. Pharmacotherapy. 2023 Sep;43(9):872-882. doi: 10.1002/phar.2830. Epub 2023 Jun 12. — View Citation

Khalefa HG, Shawki MA, Aboelhassan R, El Wakeel LM. Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study. Breast Cancer Res Treat. 2020 Aug;183(1):117-125. doi: 10.1007/s10549-020-05762-8. Epub 2020 Jun 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of chemotherapy induced-peripheral neuropathy using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria	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.	weekly for up to 8 weeks
Primary	Patient's Quality of Life	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.	at baseline, at the end of 4 weeks and at the end of 8 weeks
Secondary	Changes in serum levels of biomarker namely nerve growth factor (NGF).	measuring serum level of nerve growth factor using enzyme-linked immunoassay (ELISA) Kit.	at baseline and at end of 8 weeks
Secondary	Adverse effects of using trimetazidine in preventing Paclitaxel Induced Peripheral Neuropathy.	any adverse/ side effect will be evaluated.	at baseline and weekly up to 8 week
Secondary	Severity of chemotherapy induced-peripheral neuropathy.	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."	at baseline, at the end of 4 weeks and at the end of 8 weeks