Clinical trial NCT06459193: Trimetazidine Efficacy in Attenuating Paclitaxel-Induced Peripheral Neuropathy
Official title: Evaluation of Trimetazidine in Alleviating Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Peripheral Neuropathy Due to Chemotherapy
Keywords: Paclitaxel
Trimetazidine
quality of life
nerve growth factor
peripheral neuropathy
Lead sponsor: Minia University
Sponsor class: OTHER
First posted: 2024-06-14
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of chemotherapy induced-peripheral neuropathy using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria
timeFrame: weekly for up to 8 weeks
measure: Patient's Quality of Life
timeFrame: at baseline, at the end of 4 weeks and at the end of 8 weeks
Secondary outcomes:
measure: Changes in serum levels of biomarker namely nerve growth factor (NGF).
timeFrame: at baseline and at end of 8 weeks
measure: Adverse effects of using trimetazidine in preventing Paclitaxel Induced Peripheral Neuropathy.
timeFrame: at baseline and weekly up to 8 week
measure: Severity of chemotherapy induced-peripheral neuropathy.
timeFrame: at baseline, at the end of 4 weeks and at the end of 8 weeks
Other outcomes:
Locations:
city: Minya
country: Egypt
facility: Minia Oncology Center
Study officials:
affiliation: Clinical Pharmacy Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
name: Asmaa N. Iqbal Ahmed, Demonstrator
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Pharmacy Department, Faculty of Pharmacy, October 6 University, Giza, Egypt
name: Engy A. Wahsh, Asst. Prof.
role: STUDY_DIRECTOR
affiliation: Pharmaceutics department, Faculty of Pharmacy, Minia University, Minia, Egypt.
name: Fatma M. Mady, Professor
role: STUDY_CHAIR
affiliation: Clinical pharmacy Department, Faculty of Pharmacy, Minia University, Minia, Egypt.
name: Eman M. Sadek, Lecturer
role: STUDY_DIRECTOR
affiliation: Department of Clinical Oncology, Faculty of Medicine, Minia University, Minia, Egypt.
name: Ahmed Mostafa Abd-Elaziz, Lecturer
role: STUDY_DIRECTOR
affiliation: Department of Clinical Pathology, Faculty of Medicine, Minia University, Minia, Egypt.
name: Noha Mahmood Abd-Allah, Lecturer
role: STUDY_DIRECTOR
References:
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.
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.
citation: 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.