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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Vinca Alkaloid Adverse Reaction
• Intervention / Treatment: Drug: Loratadine; Drug: Diosmin/ Hesperidin

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 Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Noha Kamal Morsy Ibraheem, Assistant lecturer; Phone Number: +201002014552; Email: noha2010_pharma@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; 30 patients will receive Vincristine 1.5 mg/m2 (maximum: 2 mg) or Vinblastine 6 mg/m2 according to treatment protocol.
Experimental: Loratadine group; 30 patients will receive One tablet 10 mg orally once daily starting with vincristine or vinblastine administration for three cycles	Drug: Loratadine; Intervention is given to study its' effect on vinca alkaloids induced neuropathy
Experimental: diosmin 450mg / hesperidin 50 mg 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	Drug: Diosmin/ Hesperidin; Intervention is given to study its effect on vinca alkaloids induced neuropathy

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ain Shams University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: January 22, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 17, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Loratadine; neuropathy; Vinca alkaloids; Diosmin/Hespridin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dermatologic Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Histamine H1 Antagonists, Non-Sedating; Loratadine
• Other Study ID Numbers: AinShamsU2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No