Topical Erythropoietin Hydrogel in Management of Oral Lichen Planus

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the clinical efficacy of erythropoietin gel containing a solution of 4000 units with triamcinolone acetonide 0.1% gel in the treatment of symptomatic oral lichen planus (OLP)

Detailed Description
-----------------
At the first visit before the initiation of the study; Information including age, gender, disease process, medical history, drug history, family history, and clinical symptoms and signs will be documented. Patients will be examined clinically by magnifying mirror using a spotlight for the oral lesions, the distribution of the lesions and the affected areas will be recorded, and a punch biopsy will be taken to confirm the diagnosis. Twenty-four patients seeking treatment for symptomatic OLP will be assessed for eligibility for this study. Patients will be recruited from the outpatient clinic, department of Oral Medicine and Periodontology, Faculty of Dentistry, and the Department of Skin and Venereal Disease, Faculty of Medicine, Ain Shams University. The study will be conducted according to the ethical principles provided by the Declaration of Helsinki and according to the principles of good clinical practice. Faculty of Dentistry-Ain Shams University Research Ethical Committee (FD-ASU-RECD) will review the protocol, the procedure will be fully explained to the patients. Each patient will receive detailed verbal and written information about the study protocol. Understanding and agreement to enroll in the study will be confirmed and written consent forms will be obtained. II- Study design, interventions, blinding, randomization, and grouping: The study is designed as a Randomized- parallel 2 arm - assessor blinded single center- controlled comparative clinical trial with immunohistochemical analysis. Interventions The oral Gel carrier of the intervention will be designed, prepared, and in vitro characterized at the Pharmaceutical Science Department, Faculty of Pharmacy- Ain University. Patients grouping Patients who met the eligibility criteria will be randomly assigned to 2 different treatment regimens using computer-generated random tables and allocation concealment; Group I Will include twelve patients with oral lichen planus lesions receiving ( erythropoietin mucoadhesive thermosensitive hydrogel), twice daily (Experimental Arm) Group II: It will include twelve patients with oral lichen planus lesions receiving (Topical corticosteroid 0.1%) four times per day for 8 weeks (Positive control arm) In the fourth- and eighth both patients in group II will receive topical antifungal (Miconazole 2%) to avoid secondary candidiasis while patients in group I will receive topical antifungal only if needed

Official Title
-----------------
Topical Erythropoietin Hydrogel in Management of Oral Lichen Planus: A Randomized Controlled Clinical Trial

Conditions
-----------------
Oral Lichen Planus

Intervention / Treatment
-----------------
* Drug: erythropoietin
* Drug: Triamcinolone acetonide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically proven painful symptomatic forms of OLP confirmed by the presence of red or erythematous changes, or shallow ulcerations with fine lacy lines at the periphery of the lesion accentuated by stretching and not eliminated by rubbing (Wickham's striae) Histopathological proven symptomatic OLP Exclusion Criteria: History of the drug-induced lichenoid lesion. Presence of systemic conditions as; serious active or recurrent infections, malignancy, diabetes mellitus, hypertension, or significant heart, liver, or renal diseases. Assessed using a medical questionnaire guided by the Cornell Medical Index Smoking Known hypersensitivity or severe adverse effects to the treatment drugs or to any ingredient of their preparation as mentioned in history Pregnancy or breastfeeding. History of previous treatments potentially effective on OLP such as antimalarial agents, retinoids, corticosteroids, or immunosuppressive drugs from less than 2 weeks for topical medications, and 4 weeks for systemic medications before starting the study Loss of pliability or flexibility in the tissues involved by the lesions of OLP. Histological signs of epithelial dysplasia or lichenoid lesions within the biopsied sites. Patients with extensive skin lesions and indicated for systemic corticosteroids. Vulnerable groups (Handicapped, orphans, or prisoners) -

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: erythropoietin mucoadhesive thermosensitive hydrogel<br>erythropoietin solutions of 150, 300, and 500 IU/mL were mixed with trimethyl chitosan (M) solutions. glycerophosphate solution was then added to the mixture to obtain erythropoietin-loaded hydrogel comprising final concentrations of trimethyl chitosan (5%) and glycerophosphate (20%). | Drug: erythropoietin<br>* erythropoietin solutions of 150, 300, and 500 IU/mL were mixed with trimethyl chitosan (M) solutions. glycerophosphate solution was then added to the mixture to obtain erythropoietin-loaded hydrogel comprising final concentrations of trimethyl chitosan(5%) and glycerophosphate (20%).<br>* Other names: erythropoietin mucoadhesive thermosensitive hydrogel;|
| Active Comparator: Triamcinolone Mucoadhesive gel<br>Each 0.1 mg triamcinolone acetonide in a dental paste containing gelatin, pectin, cream flavor, vanilla flavor and carboxymethylcellulose sodium in Plasticized Hydrocarbon Gel, a polyethylene and mineral oil gel base. | Drug: Triamcinolone acetonide<br>* Each 0.1 mg triamcinolone acetonide in a dental paste containing gelatin, pectin, cream flavor, vanilla flavor and carboxymethylcellulose sodium in Plasticized Hydrocarbon Gel, a polyethylene and mineral oil gel base.<br>* Other names: Triamcinolone Mucoadhesive gel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Scoring | The marker lesion in each patient will be assessed for areas of reticulation, erosion, and ulceration by visual examination and the scoring will be recorded as follow: 0: Mild represented no lesion/normal mucosa. White striae/no erythematous area. White striae with atrophic area less than 1 cm2 White striae with atrophic area of more than 1 cm2 White striae with an erosive area less than 1 cm2 White striae with an erosive area of more than 1cm2 | The assessment will be carried out at baseline, 1 month and 2 months after starting the treatment protocol and then at 3 months after the end of the observational period | 
| Visual Analogue Score | The Visual Analogue Score consisted of a 10-cm horizontal line marked 0-10 (0 no pain; 10 most severe pain experienced). Patients will mark the scale at each visit. The Visual Analogue Score is then scored by measuring from the patient's mark to the beginning of the scale in cm, and all Visual Analogue Score will be included on one sheet of paper allowing the patient to think in terms of change instead of absolutes. | The assessment will be carried out at baseline, 1 month and 2 months after starting the treatment protocol and then at 3 months after the end of the observational period | 
| Imaging and measuring surface area of the oral lesion | Standardized photographs of the oral marker lesion for each patient will be taken with the same digital camera and setting, and the surface area of the lesion will be outlined and measured using specific image software. | The assessment will be carried out at baseline, 1 and 2 months after starting the treatment protocol and then at 3 months after the end of the observational period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor necrosis factor Salivary level | The patient will export 10 ml of unstimulated whole saliva into a sterile centrifuge. tube. The saliva will be centrifuged, filtered, and frozen until use. The mean concentration of TNF-α in the whole saliva of in patients with OLP lesions will be measured by ELISA kit. The assay will be performed according to the manufacturer's instruction The patient will export 10 ml of unstimulated whole saliva into a sterile centrifuge. tube. The saliva will be centrifuged, filtered, and frozen until use. The mean concentration of TNF-α in the whole saliva of in patients with OLP lesions will be measured by ELISA kit. The assay will be performed according to the manufacturer's instruction | The Salivary Sample for each patient will be taken at baseline and after 2 months treatment period. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
erythropoietin gel, tumor necrosis factor, oral lichen planus