Rebamipide (Regular & Nanoparticulated) vs. Clobetasol in Management of Methotrexate-Induced Oral Ulceration in Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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The aim of this intervention study is to compare the effect of topical Rebamipide (regular and nanoparticulated) to topical Clobetasol propionate in management of Methotrexate induced oral mucositis in patients with rheumatoid arthritis.

Detailed Description
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A random sample of patients diagnosed with rheumatoid arthritis attending at the Rheumatology clinic in faculty of Medicine, Cairo University Hospital, will be enrolled by the investigator in the study in a consecutive order after being examined for methotrexate induced oral ulceration by means of history and clinical examination. Since oral mucositis associated with Methotrexate include production of free radicals, increase of inflammatory cytokines, and alteration of intracellular signal transduction, this suggests that Rebamipide should be useful for its treatment and prevention. Thus, this RCT will be the first to evaluate the treatment of Methotrexate-induced oral mucositis using Rebamipide and Rebamipide nanoparticles in patients with rheumatoid arthritis.

Official Title
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Evaluation of Topical Rebamipide Versus Topical Clobetasol in Management of Methotrexate-Induced Oral Ulceration in Rheumatoid Arthritis Patients: Randomized-Controlled Clinical Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Rebamipide
* Drug: Nanoparticulated Rebamipide
* Drug: Clobetasol Propionate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who agreed to sign the informed consent. Age: 20-70 years old. Gender: males and females RA patients treated with MTX and suffering from MTX-induced oral ulceration. Exclusion Criteria: Patients refused to sign the informed consent. Pregnant or lactating females in their child bearing age group. patients with known or suspected history of hypersensitivity to any of the ingredients of the preparation of the drugs used. Systemic disease: such as uncontrolled diabetes mellitus, auto-immune diseases known to cause oral ulceration, renal or liver dysfunction or any other condition considered risky by the clinician. Patients treated with any medication for the condition at the time of setting. Salivary gland diseases. Malignancy.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rebamipide<br>The enrolled subjects will be treated with Rebamipide in mucoadhesive gel for 2 weeks or until complete healing. | Drug: Rebamipide<br>* A mucosal protection drug developed in Japan for the treatment of gastritis and gastric ulcer.<br>* Other names: Mucosta;|
| Experimental: Nanoparticulated Rebamipide<br>The enrolled subjects will be treated with nanoparticulated Rebamipide in mucoadhesive gel for 2 weeks or until complete healing. | Drug: Nanoparticulated Rebamipide<br>* A mucosal protection drug developed in Japan for the treatment of gastritis and gastric ulcer will be used in nanotechnology.<br>* Other names: Mucosta;|
| Active Comparator: Clobetasol<br>The enrolled subjects will be treated with Clobetasol in mucoadhesive gel for 2 weeks or until complete healing. | Drug: Clobetasol Propionate<br>* A corticosteroid drug used as a gold standard for treatment of methotrexate induced oral ulceration.<br>* Other names: corticosteroids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the Clinical improvement of oral ulcers | Will be assessed using World Health Organization (WHO) grading of mucositis | assessment will be at baseline, 2 weeks and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective degree of pain | All patients were introduced to the Numerical Rating Scale (NRS) and learnt how to express their pain through it, patients were instructed to fill the scale paper at the first visit [baseline], this procedure was repeated for each follow-up visit. | Pain assessment will be daily for the first week then at 2 weeks and 4 weeks. | 
| size of oral ulcer | The ulcer size was determined by measuring the distance between two opposite edges of the ulcer border, using a periodontal probe in millimeters. | assessment at 0, 2 weeks and 4 weeks | 
| healing time of the ulcer | The total healing time of oral ulcers Will be recorded in days for all the patients. | assessment at 0, 2 weeks and 4 weeks |