Comparing Diosmin-Hesperidin and Loratadine to Prevent Bone Pain From G-CSF in Patients With Blood Cancers

December 25, 2025 updated by: Alexandria University

A Comparative Study of Diosmin-Hesperidin and Loratadine for the Prevention of G-CSF Induced Bone Pain in Patients With Hematological Malignancies

This is a comparative interventional study to determine the best way to prevent G-CSF induced bone pain in patients with hematological malignancies (blood cancers). G-CSF (Granulocyte Colony-Stimulating Factor) is a drug commonly used in these patients to boost white blood cell production, but it frequently causes severe bone pain.

The study is comparing two oral medications for their effectiveness as a preventive treatment:

  • Diosmin-Hesperidin (a flavonoid supplement).
  • Loratadine (a common anti-allergy medication).

The core question the study is trying to answer is:

  • Is diosmin-hesperidin effective in preventing G-CSF-induced bone pain compared to loratadine?
  • Does the combination of diosmin-hesperidin and loratadine offer better pain prevention than either drug alone?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, controlled, randomized, and open-label clinical trial conducted at Alexandria University Hospitals to compare the efficacy of diosmin-hesperidin versus loratadine, and their combination, for the prevention of G-CSF-induced bone pain in adult patients (18-65 years) with hematological malignancies (leukemia or lymphoma) receiving filgrastim.

Rationale:

G-CSF-induced bone pain is a common and debilitating side effect, impacting patient quality of life. While current management strategies using NSAIDs and antihistamines are not always sufficient, diosmin, a flavonoid with known anti-inflammatory and neuroprotective properties, has not been thoroughly investigated for this indication. This study aims to address this gap and explore the potential of diosmin, loratadine, and their combination to mitigate G-CSF-induced bone pain.

Study Design:

Participants meeting the eligibility criteria (detailed elsewhere) will be randomly assigned to one of four treatment groups:

Control Group: No specific treatment for bone pain. Loratadine Group: Loratadine 10mg tablet once daily, administered 30 minutes before filgrastim and continued for 5 days.

Diosmin-Hesperidin Group: Diosmin-Hesperidin 500mg tablet twice daily, administered 30 minutes before filgrastim and continued for 5 days.

Combination Group: Loratadine 10mg tablet once daily plus Diosmin-Hesperidin 500mg tablet twice daily, administered 30 minutes before filgrastim and continued for 5 days.

Filgrastim will be administered according to standard clinical practice for the underlying hematological condition.

Assessments:

Baseline Assessment: Before the start of filgrastim administration, demographic data, medical history (including type of malignancy, comorbidities, prior G-CSF treatment, and chemotherapy details), baseline laboratory tests (CBC, CRP, liver and kidney function), and baseline pain assessment using the Brief Pain Inventory (BPI) will be collected.

Follow-up Assessments:

Within 24 hours of the first filgrastim dose, pain will be assessed using the BPI, and baseline TNF-alpha levels will be measured.

After 5 days of treatment, follow-up laboratory tests (including TNF-alpha levels) and pain assessment using the BPI will be conducted.

Primary Outcome:

The primary outcome is to compare the effectiveness of diosmin-hesperidin, loratadine, and their combination in preventing G-CSF-induced bone pain. This will be assessed by changes in pain frequency and severity (measured by the BPI) and changes in serum TNF-alpha levels.

Secondary Outcome:

The secondary outcome is to identify risk factors associated with the frequency and severity of G-CSF-induced bone pain.

Statistical Analysis:

Data will be analyzed using IBM SPSS version 26. Appropriate statistical tests will be used to compare the treatment groups and assess the relationships between variables.

Ethical Considerations:

The study will be conducted in accordance with the Declaration of Helsinki and will be subject to approval by the Ethics Committee of Alexandria University. All participants will provide written informed consent before enrollment.

Study Type

Interventional

Enrollment (Estimated)

88

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
      • Alexandria, Egypt, 21532
        • Recruiting
        • Alexandria University Hospitals
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults 18 to 65 years old
  • Receiving a G-CSF for one of the following indications:

Treatment of neutropenia along with treatment for leukemia or lymphoma Neutropenia prevention following autologous hematopoietic cell transplant

  • Patients with or without bone pain associated with G-CSF administration.
  • Willingness to provide informed consent to participate in the study.

Exclusion Criteria:

  • Patients with solid tumors.
  • Pregnant or breastfeeding women.
  • Patients with known allergies or hypersensitivity to Loratadine, Diosmin- Hespiridin or Filgrastim.
  • Patients with pre-existing bone disorders or receiving bone modifying agents
  • Chronic use of antihistamines, Diosmin-Hespiridin, NSAIDs, corticosteroids, or immunosuppressants.
  • Receiving medications with drug interaction grade X with Loratadine, Diosmin-Hespiridin or Filgrastim
  • Patients who are unable to understand or provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Participants in this arm will receive standard supportive care for G-CSF-induced bone pain, but will not receive the study interventions (loratadine or diosmin-hesperidin).
Active Comparator: Intervention
Participants in this arm will receive loratadine 10mg tablets once daily, 30 minutes before filgrastim administration, for 5 days.
Drug: Loratadine
Loratadine 10 mg oral tablet administered once daily, starting 30 minutes before filgrastim administration and continued for 5 consecutive days.
Experimental: Diosmin-Hesperidin
Participants in this arm will receive diosmin-hesperidin 500mg tablets twice daily, 30 minutes before filgrastim administration, for 5 days.
Drug: Diosmin-Hesperidin
Diosmin-Hesperidin 500 mg oral tablet administered twice daily, starting 30 minutes before daily filgrastim administration and continued for 5 consecutive days.
Experimental: Loratadine + Diosmin-Hesperidin
Participants in this arm will receive loratadine 10mg tablets once daily plus diosmin-hesperidin 500mg tablets twice daily, 30 minutes before filgrastim administration, for 5 days.
Drug: Loratadine + Diosmin-Hesperidin
Combination of Loratadine 10 mg oral tablet once daily plus Diosmin-Hesperidin 500 mg oral tablet twice daily, starting 30 minutes before daily filgrastim administration and continued for 5 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone Pain Severity (Brief Pain Inventory)
Time Frame: Baseline (before first dose of Filgrastim), 24 hours after first Filgrastim dose, and 5 days after treatment initiation.

This will be measured using the validated Brief Pain Inventory (BPI), which assesses pain intensity (e.g., worst pain, average pain). BPI pain severity will be compared for each trial arm. BPI pain severity will be compared as a composite score (sum of individual pain values divided by 4).

A score ranging from 0 (no pain) to 10 (worst pain imaginable).
Baseline (before first dose of Filgrastim), 24 hours after first Filgrastim dose, and 5 days after treatment initiation.
Bone Pain Interference (Brief Pain Inventory)
Time Frame: Baseline (before first dose of Filgrastim), 24 hours after first Filgrastim dose, and 5 days after treatment initiation.

This will be measured using the validated Brief Pain Inventory (BPI), which assesses the degree to which pain interferes with daily life. BPI pain Interference will be compared for each trial arm. BPI pain interference will be compared as a composite score (sum of individual pain interference values divided by 7).

A scale of 0 (does not interfere) to 10 (completely interferes).
Baseline (before first dose of Filgrastim), 24 hours after first Filgrastim dose, and 5 days after treatment initiation.
Change in Serum Tumor Necrosis Factor-alpha (TNF-alpha) Levels
Time Frame: 24 hours after first Filgrastim dose, and After 5 days of the intervention period
Serum TNF-alpha (pg/mL) is an inflammatory cytokine level measured in the blood that is hypothesized to be elevated in G-CSF induced bone pain. The change from baseline levels will be compared across the four study arms to determine the biological effect of the interventions. Lower levels of TNF-alpha are indicative of a reduction in the inflammatory response.
24 hours after first Filgrastim dose, and After 5 days of the intervention period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexandria University

Investigators

  • Principal Investigator: Mai Moustafa Helmy, Professor, Alexandria University
  • Principal Investigator: Omar Mohamed Ghallab, Professor, Alexandria University
  • Principal Investigator: Reham AbdelHalem Abo Elwafa, Professor, Alexandria University
  • Principal Investigator: Noha Alaa Eldin Hamdy, Assistant professor, Alexandria University
  • Principal Investigator: Mayssaa Mohamed Elsayed, pharmD, Alexandria University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2025

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

December 1, 2025

First Submitted That Met QC Criteria

December 18, 2025

First Posted (Estimated)

December 24, 2025

Study Record Updates

Last Update Posted (Actual)

December 29, 2025

Last Update Submitted That Met QC Criteria

December 25, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB NO:00012098
  • Serial Number: 0108746 (Other Identifier: Ethics Committee Faculty of Medicine Alexandria University)
  • FWA Number: 00018699 (Other Identifier: Ethics Committee Faculty of Medicine Alexandria University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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