Pimecrolimus and Epidermal Barrier Function
This study seeks to investigate the role of pimecrolimus in restoring disturbed skin barrier function and reversing epidermal abnormalities found in atopic dermatitis (AD). The project is based on findings the investigators presented at the recent SID meeting in Providence and published in the J Invest Dermatol (122: 1423-31, 2004). The investigators research shows that AD is characterized by impaired skin barrier function, reduced stratum corneum hydration, impaired epidermal lipid composition and epidermal differentiation. In this proposed project, the investigators wish to examine the influence of pimecrolimus and betamethasone valerate on transepidermal water loss (TEWL) as a marker of the skin barrier function, on stratum corneum hydration, on stratum corneum lipid content and on epidermal differentiation regarding keratins and cornified envelope proteins in AD patients. The study involves biophysical measurements of TEWL and skin hydration, lipid analysis, immuno-histochemistry, Western blotting and micro array techniques. This study shall clarify whether pimecrolimus restores the epidermal barrier and whether this contributes to the beneficial effect of pimecrolimus on AD.
To explore the stratum corneum hydration, transepidermal water loss, capacity for barrier repair and the integrity of the stratum corneum in patients treated with 1 % pimecrolimus cream when applied twice a day to atopic dermatitis of the upper limbs, and to access the substance's influences on the epidermis through histological, ultra-structural, and biochemical analysis using punch biopsies from day 1 of one arm and day 22 from both treated arms. 0.1 % betamethasone valerate cream b.i.d will be used as a control treatment.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Role for Pimecrolimus in Restoring Skin Barrier Function and Normalizing Epidermal Lipid Content and Differentiation in Atopic Epidermis: a Randomized, Intra-patient, Double-blind (Right/Left Arm) Study in Adults With Atopic Dermatitis Treated With 1 % Pimecrolimus Cream and 0.1 % Betamethasone Cream as Treatment Control Twice Daily for 3 Weeks|
- To explore the effect of 1 % pimecrolimus cream on the epidermis in adults with AD [ Designated as safety issue: No ]
To explore the effect of 1 % pimecrolimus cream on the epidermis in adults with AD (with 0.1 % betamethasone serving as control) by testing the hypothesis that:
- 1 % pimecrolimus cream leads to a reduction of biophysical parameters of AD representing the permeability barrier of the skin after three weeks of treatment.
- To explore the epidermal effect on proliferation rate, differentiation, and stratum corneum lipid content.
- To explore the effect of 1 % pimecrolimus cream induced changes in ultra-structure and gene expression in the epidermis [ Designated as safety issue: No ]
- To explore the effect of 1 % pimecrolimus cream induced changes in ultra-structure and gene expression in the epidermis.
- To compare the key protein molecules of keratinocyte growth and differentiation and their gene expression in relationship to clinical skin improvement.
|Study Start Date:||March 2005|
|Experimental: Pimecrolimus cream treatment||Drug: cream treatment|
|Active Comparator: Betamethasone valerate cream treatment||Drug: cream treatment|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01132079
|Dept. of Dermatology, University of Kiel|
|Kiel, Germany, 24105|
|Principal Investigator:||Ehrhardt Proksch, MD, PhD||Dept. of Dermatology, University of Kiel|