Clinical and Immunohistochemical Effect of Topical Pimecrolimus in Treatment of Oral Lichen Planus

NCT ID: NCT02443311

Last Updated: 2015-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2012-08-31

Brief Summary

Oral lichen planus (OLP) is a chronic disease characterized by periods of remission and relapse. Therapeutic objectives for OLP should be to quickly reduce disease symptoms by targeting pathophysiological pathways, and to provide long-term management by reducing recurrences. Pimecrolimus is a novel topical selective inflammatory cytokine release inhibitor; considering its mechanism of action it is reasonable to theorize that pimecrolimus may effectively treat OLP without the potential side effects that are associated with corticosteroids.

Detailed Description

Lichen planus is a chronic, immunological, mucocutaneous disease, characterized by periods of remission and relapse1. Oral lichen planus (OLP) is one of the most common mucocutaneous diseases manifesting in the oral cavity, and the oral mucosa may be the only site of involvement 2, with variable incidence between 0.5% and 4% 3. Three major clinical forms of OLP (reticular, erosive/ ulcerative, and erythematous/atrophic) have been recognized, which could alternate and overlap in a dynamic state as disease progresses. Ulceration is the most severe form that it interferes with eating, speech, and swallowing. Erosive OLP lasts for years, resistance to treatment and spontaneous remissions are rare 4,5. Oral lichen planus is a T-cell-mediated chronic inflammatory oral mucosal disease. Both antigen-specific and non-specific mechanisms may be involved in the pathogenesis of OLP. Antigen-specific mechanisms include antigen presentation by basal keratinocytes to CD4+ helper T-cells that are stimulated to secrete the T helper -1 cytokines IL-2 and IFN-γ. Subsequently, CD8+ cytotoxic T-cells may be activated which then trigger basal keratinocyte apoptosis in OLP. While, non-specific mechanisms include mast cell degranulation and matrix metalloproteinase (MMP) activation in OLP lesions 6. The best known treatment of OLP remains high-potency topical corticosteroids7. However, corticosteroids are known to induce local atrophy, fragility, and telangiectasias, and to promote infections, including acute candidiasis. They also have theoretical risks of lowering local immunity, corticosteroids can exert their effects on the immune system by modulating transcription of genes in cells involved in immune response and other cell types; therefore this mode of action is not selective for the pathogenesis of lichen planus 8-10. A recent Cochrane review showed only little evidence for superiority of the assessed interventions over placebo for palliation of symptomatic OLP and recommended the need of randomized clinical trials on new therapies 11. Pimecrolimus a novel topical selective inflammatory cytokine release inhibitor; that binds to intra-cytoplsmic protein (macrophillin-12) subsequently inhibiting dephosphorylation of nuclear factor of activated T cells by calcineurin; this markedly reduces T-cell cytokine production. Given the T-cell-mediated pathogenesis of OLP, application of this calcineurin inhibitor seems to be a promising therapeutic option 12-14. Several case studies and open-label trials used topical pimecrolimus in treatment of OLP reported beneficial effects 12,15. Few prospective, randomized, vehicle-controlled studies have also been conducted and proved benefit of pimecrolimus over placebo 16,10,17. And one recent prospective study compared the effect of topical pimecrolimus with topical corticosteroid in treatment of OLP 18. The purpose of this study was to compare the effectiveness of topical pimecrolimus 1% with topical corticosteroid, in the treatment of oral erosive and atrophic lichen planus as a prospective, comparative clinical trial.

Conditions

Oral Lichen Planus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group I

Pimecrolimus 1% cream (Elidel, Novartis Pharmaceuticals, East Hanover, NJ)+ custom made hydrophilic Adhesive gel base (Department of Pharmaceutics and Industrial Pharmacy. Faculty of Pharmacy. Ain Shams University) 4 Times/day for 4 weeks

Group Type: EXPERIMENTAL

Pimecrolimus 1% cream

Intervention Type: DRUG

Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.

Group II

Betamethasone 17-valerate 0.1% cream (Betnovate, GlaxoSmithKline, Cairo, Egypt)+ custom made hydrophilic Adhesive gel base (Department of Pharmaceutics and Industrial Pharmacy. Faculty of Pharmacy. Ain Shams University) 4 Times/day for 4 weeks

Group Type: ACTIVE_COMPARATOR

Betamethasone 17-valerate 0.1% cream

Intervention Type: DRUG

Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.Topical antifungal Miconazole 2% gel (Miconaz, oral Medical Union Pharmaceutical, Cairo, Egypt) was applied only in the fourth week of treatment period to avoid secondary candidiosis

Interventions

Pimecrolimus 1% cream

Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.

Intervention Type: DRUG

Betamethasone 17-valerate 0.1% cream

Patients were instructed to apply a thin layer of mixed equal amounts (½ ml) of the study medication and the adhesive gel base per application guided by the graduation on the plastic syringe on the oral lesions, 4 times daily, for a total of 1month. The patients were asked not to eat, drink, for 30 minutes after each application.Topical antifungal Miconazole 2% gel (Miconaz, oral Medical Union Pharmaceutical, Cairo, Egypt) was applied only in the fourth week of treatment period to avoid secondary candidiosis

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• clinically and histologically confirmed painful Erosive or Atrophic OLP
• free from any systemic diseases using medical questionnaire guided by Cornell Medical Index

Exclusion Criteria

• history of drug induced lichenoid lesions
• potential treatment of OLP for less than 2 weeks by topical and 4 weeks systemic therapy before study start
• pregnant or breast-feeding women,
• smoking and
• known hypersensitivity or severe adverse effects to the treatment drugs or to any ingredient of their preparation
• loss of paliability or flexibility in the tissues involved by the oral lesions or histological signs of epithelial dysplasia or lichenoid lesions within the biopsied sites.

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Ola Mohamed Ezzatt

Lecturer of oral medicine and periodontology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

FDASU-RECD 1214401

Identifier Type: -

Identifier Source: org_study_id