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

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT02443311

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Oral Lichen Planus	Drug: Pimecrolimus 1% cream Drug: Betamethasone 17-valerate 0.1% cream	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Comparative Clinical and Immunohistochemical Study Between Topical Pimecrolimus and Corticosteroid in Treatment of Oral Lichen Planus

Study Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: 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.
Active Comparator: 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	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

Arm

Intervention/Treatment

Experimental: 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

Drug: Pimecrolimus 1% cream

Active Comparator: 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

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

Outcome Measures

Primary Outcome Measures

clinical scoring (CS) [2 months/ once per week for one months then after 2 months]
0 represented no lesion/normal mucosa; 1, mild white striae/no erythematous area; 2, white striae with atrophic area less than 1 cm²; 3, white striae with atrophic area more than 1 cm²; 4, white striae with erosive area less than 1 4 cm²; and 5, white striae with erosive area more than 1 cm²
visual analog scale (VAS) [2 months/ once per week for one months then after 2 months]
Patients also ranked the severity of pain and burning sensation on 100-mm visual analog scale

Secondary Outcome Measures

CD4+,CD8+, CD133 [baseline and after 1 month treatment]
Immunohistochemical analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.