The Efficacy of Erythropoietin Oral Gel Versus Erythropoietin Mouthwash in the Management of Recurrent Aphthous Stomatitis

The Efficacy of Erythropoietin Oral Gel Versus Erythropoietin Mouthwash in the Management of Recurrent Aphthous Stomatitis: A Randomized Controlled Clinical Study With Biochemical Analysis

Erythropoietin (EPO) exerts anti-inflammatory effects by inhibiting NF- kappa B-dependent formation of pro-inflammatory cytokines, thus it reduces local and circulating levels of these disease (recurrent aphthous stomatitis RAS) related cytokines. So, it is considered as a potent anti-inflammatory cytokine in inflammatory disorders and infectious disease. It also accelerates wound-healing and decreases the extent of apoptosis and the areas of the open wound. this drug seems to be a promising therapeutic option in oral lesions. the effectiveness of EPO oral gel and EPO mouth wash were compared on patients with recurrent aphthous stomatitis and investigated therapeutic mechanism by examining treatment effect on expression of IL-2 IN RAS.

Study Overview

• Status: Completed
• Conditions: Recurrent Aphthous Stomatitis
• Intervention / Treatment: Drug: Epoetin 4000; Other: Placebo

Detailed Description

Sixty patients with recurrent aphthous stomatitis were randomly assigned into three equal groups to receive topical Erythropoietin oral gel four times per day (after meals and at bedtime) (Group I).

Erythropoietin mouthwash 4 times per day (after meals and at bedtime) (Group II), and placebo isotonic (normal saline) with concentration 0.90% of sodium chloride (NaCl) (Group III).

All patients were followed up four 1 week, photographs were taken at the beginning and end of the treatment.

patients were assessed using pain visual analogue scale (PVAS), clinical assessments for the size of the ulcers and rate of their recurrence.

pretreatment and post treatment salivary samples were taken to detect the expression and levels of salivary IL-2.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governorate
    • New Cairo, Cairo Governorate, Egypt, 4710001
      • Future University in Egypt

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients should be free from any systemic disease or Behcet syndrome.
• Patients ≥18 years of age, male or female are eligible.
• Oral pain score of 4 or higher on a scale of 0-10 with 0 representing no pain in the presence of oral ulceration.
• Patient has only aphthous ulcer and It should had not been passed more than 4 days from beginning of their ulcer.

Exclusion Criteria:

• • Patients with poor oral hygiene or not willing to perform oral hygiene measures.

  • Smoking and alcohol use.
  • Pregnant and lactating females
  • Patients with history of any topical or systemic medication or steroid therapy 1 month prior to the investigation.
  • The vulnerable group; prisoners, mentally or physically disabled patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erythropoietin/oral gel; topical erythropoietin oral gel 4 times daily for 1 week	Drug: Epoetin 4000; Erythropoietin hormone
Experimental: placebo; isotonic (normal saline) with concentration 0.90% of sodium chloride (NaCl) 4 times daily	Other: Placebo; isotonic (normal saline) with concentration 0.90% of sodium chloride (NaCl) 4 times daily
Experimental: Erythropoietin/mouthwash; Erythropoietin mouthwash 4 times daily for 1 week	Drug: Epoetin 4000; Erythropoietin hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain visual analogue scale (P-VAS)	The pain VAS consisted of a 10-cm horizontal line marked 0-10 (0 no pain, 10 most severe pain experienced). Patients marked the scale at each visit, and the all P-VAS were included on one sheet of paper allowing the patient to think in terms of change instead of absolutes. The P-VAS was then scored by measuring from the patient's mark to the beginning of the scale in cm.	Reduction from baseline and after 1 week of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Size of the ulcer	The score corresponds to the average diameter of the ulcers in millimeters, that is, a patient having ulcers of average size of 5 mm would score 5. Patients indicated the average size of their ulcers on a diagram of different diameter circles. The maximum score was 20 to accommodate the small number of RAS cases in which ulcers are on average more than 10 mm in diameter.	change from baseline and after 1 week of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical analysis	Salivary IL-2 was detected by an Enzyme-Linked Immunosorbent Assay (ELISA). This sandwich kit is for the accurate quantitative detection of Human Interleukin 2 (also known as IL-2) in serum, plasma, cell culture supernates, Ascites, tissue homogenates or other biological fluids.	From baseline and after 1 week of treatment

Collaborators and Investigators

• Sponsor: Future University in Egypt
• Investigators: Study Director: Mai T. assistant lecturer Mai T. Elgendi, Assistant lecturer, Faculty of oral medicine- Future University in Egypt

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Actual): December 21, 2024
• Study Completion (Actual): February 27, 2025

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: April 4, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Erythropoietin; IL-2; Recurrent aphthous stomatitis
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Stomatitis; Stomatitis, Aphthous; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: FDAsu-Rec ID032209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: the age and number of the participants
• IPD Sharing Time Frame: will be available in September 2025
• IPD Sharing Access Criteria: other researchers in oral medicine will be able to access, when the experiment is published internationally
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

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