Evaluation of The Effect of Loratadine Versus Diosmin/Hesperidin Combination on Vinca Alkaloids Induced Neuropathy

Phase 3

• Conditions: Vinca Alkaloid Adverse Reaction
• Interventions: Drug: Diosmin/ Hesperidin; Drug: Loratadine

• Registration Number: NCT05243706
• Lead Sponsor: Ain Shams University

Brief Summary

All vinca alkaloids causes neuropathy. The incidence of peripheral neuropathy is 30 %-40 % in patients treated with vincristine. The incidence of long term neurological adverse events from vinblastine ranged from 50% to 97%. In this study, the investigators will study the effect of using either loratadine or diosmin 450mg/ hesperidin 50 mg combination on neuropathy caused by Vinca alkaloids therapy. This study is a prospective, controlled, randomized, interventional and open-label clinical trial.

Detailed Description

Ninety patients will be randomly assigned to three groups as follows:

Group 1 (Control group): 30 patients will receive Vincristine 1.5 mg/m2 (maximum: 2 mg) or Vinblastine 6 mg/m2 according to treatment protocol.

Group 2 (Loratadine group): 30 patients will receive One tablet 10 mg orally once daily starting with vincristine or vinblastine administration for three cycles.

Group 3 (hesperidin 50 mg/diosmin 450mg group): 30 patients will receive 50 mg Hesperidin and Micronized purified flavonoid fraction (MPFF) 450 diosmin combination one film coated tablet orally twice daily starting with vincristine or vinblastine administration for three cycles .

Vincristine or Vinblastine dose will be adjusted as follows: Serum bilirubin 1.5 to 3 mg/dL or transaminases 2 to 3 times ULN or alkaline phosphatase increased: Administer 50% of dose.

Treatment allocation will follow a predefined randomization list and it will be computer generated.

Study Timeline

• Study First Submitted: 2022-01-22
• Status Verified: 2022-02
• Study First Submitted QC: 2022-02-14
• Last Update Submitted: 2022-02-14
• Study First Posted: 2022-02-17
• Last Update Posted: 2022-02-17
• Study Start: 2022-03-01
• Primary Completion: 2023-09-30
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Patients prescribed vincristine or vinblastine according to standard protocols.
2. Adult patients older than18 years.
3. Patients willing to participate in the study and sign the informed consent.
4. Adequate bone barrow function (platelet count> 150 *103per microliter, absolute neutrophil count> 500 per microliter)
5. Eastern cooperative oncology group (ECOG) performance status Grade 0-2

Exclusion Criteria

1. Hypersensitivity or contraindication to loratadine, hesperidin or diosmin combination or any component of the formulation.
2. Pre-existence or history of peripheral neuropathy due to a cause different from Vinca alkaloids induced neuropathy.
3. Receiving any other medication known to cause neuropathy.
4. Receiving medications with drug interaction grade X with Loratadine as Thalidomide, Tiotropium or Orphenadrine.
5. Women of childbearing potential not using an effective contraceptive method.
6. Pregnancy or breastfeeding.
7. Inability to understand patients' information and informed consent form.
8. Severe hepatic impairment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
diosmin 450mg / hesperidin 50 mg group	Diosmin/ Hesperidin	30 patients will receive 50 mg Hesperidin and Micronized purified flavonoid fraction (MPFF) 450 diosmin combination one film coated tablet orally twice daily starting with vincristine or vinblastine administration for three cycles
Loratadine group	Loratadine	30 patients will receive One tablet 10 mg orally once daily starting with vincristine or vinblastine administration for three cycles

Primary Outcome Measures

Name	Time	Method
Assessing the efficacy of loratadine or diosmin 450mg/ hesperidin 50 mg on pain quality (i.e. sensory and pain) of Vinca alkaloids neuropathy compared to routine practice.	At baseline and after three cycles of vinca alkaloids (each cycle is 28 days)	Neuropathic Pain in 4 questions (DN4) change from baseline to after three cycles of vinca alkaloids therapy
Assessing the efficacy of loratadine or diosmin 450mg/ hesperidin 50 mg on symptoms of peripheral neuropathy of Vinca alkaloids compared to routine practice.	At baseline and after three cycles of vinca alkaloids (each cycle is 28 days)	Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) change from baseline to after three cycles of vinca alkaloids therapy
Assessing the efficacy of loratadine or diosmin 450mg/ hesperidin 50 mg on development of Vinca alkaloids neuropathy compared to routine practice.	At baseline and after three cycles of vinca alkaloids (each cycle is 28 days)	Measuring Peripheral blood Neurofilament Proteins and IL-1 beta change from baseline to after three cycles of vinca alkaloids therapy
Assessing the efficacy of loratadine or diosmin 450mg/ hesperidin 50 mg on neuropathy pain intensity of Vinca alkaloids neuropathy compared to routine practice.	At baseline and after three cycles of vinca alkaloids (each cycle is 28 days)	Measure of average pain intensity assessed by Numeric Pain Rating Scale (NS) change from baseline to after three cycles of vinca alkaloids therapy

Secondary Outcome Measures

Name	Time	Method
Evaluating the effect of loratadine versus diosmin 450mg/hesperidin 50 mg on the time to onset of neuropathy caused by Vinca alkaloids compared to control group.	from baseline to after Three cycles of vinca alkaloids (each cycle is 28 days)	Measure the time of neuropathy onset in patients
Evaluating the Number of participants with Adverse Events of loratadine versus hesperidin 50 mg/diosmin 450mg by monitoring patients for undesirable effects	from baseline to after Three cycles of vinca alkaloids (each cycle is 28 days)	The number of patients developing neuropathy as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)