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Pimecrolimus and Epidermal Barrier Function

26 mai 2010 mis à jour par: University of Kiel

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

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.

Objectives:

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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

15

Phase

  • N'est pas applicable

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

      • Kiel, Allemagne, 24105
        • Dept. of Dermatology, University of Kiel

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Subjects may be included only if the following apply at the baseline visit (day 0, before first application of study medication).

Patients to be included are:

  • Males and females of any race.
  • >= 18 years old.
  • Have atopic dermatitis as defined by Hanifin and Rajka criteria.
  • History of mild to moderate atopic dermatitis
  • At least 10 % of each upper limb affected by atopic dermatitis excluding the surface area of the hands, as these will not be treated in order to avoid cross-contamination. As reference: one hand (palm and fingers) corresponds to 10% of patient's upper limb surface.
  • One specific, representative area of the disease on each upper limb with similar size and severity on both upper limbs. These will be considered the target lesions.
  • A target lesion score of at least 3 to 8 (on a scale of 0-12) for both right and left target lesions and not differing more than 1 score point between the right and left sides.
  • be able to suspended treatment of atopic dermatitis with other therapies for the duration of the study (4-6 weeks).
  • Must be informed of study procedures and have signed the informed consent form approved for the study.

Exclusion Criteria:

Females:

  • Who are pregnant or breastfeeding.
  • Who are menstruating, capable of becoming pregnant and not practicing a medically approved method of contraception. "Medically approved" contraceptive may, at the discretion of the investigator, include abstinence. (If patients are on oral contraceptives, they must have begun treatment at least one month prior to baseline and continue at least four weeks after the last treatment).

Other therapies/medications:

  • Prior phototherapy or systemic therapy known to or suspected to have an effect on atopic dermatitis within 14 days prior to first application of study medication. Patients on a low stable dose of inhaled steroids (dose known to have negligible systemic absorption) and systemic antihistamines may participate.
  • Topical therapy known to or suspected to have an effect on atopic dermatitis (including topical steroids, topical tacrolimus ointment or topical pimecrolimus cream) on the upper limbs within 7 days prior to first application of study medication.
  • Topical therapy known to or suspected to have an effect on atopic dermatitis on other areas than upper limbs if total body surface treated is higher than 20% (due to the higher risk of systemic absorption affecting the lesions of the upper limbs) within 7 days prior to first application of study medication

Concurrent diseases / conditions and history of their diseases / conditions:

  • Patients who have signs of skin atrophy and corticoid damage on the target areas
  • Patients who are immunocompromised (e.g. lymphoma, AIDS, Wiskott-Aldrich Syndrome)
  • Patients who have concurrent skin disease (e.g. impetigo) on or near the study area which could interfere with study evaluations
  • Patients who have acute viral skin infections (e.g. herpes simplex, varicella zoster) Investigational drug / therapy use.
  • Patients who have used investigational drugs within 8 weeks prior to first application of study medication or intend to use other investigational drugs during the course of the study Ingredient hypersensitivity
  • Patients with known hypersensitivity to any ingredient of the study medication (see technical information sheet) Compliance / reliability / investigator judgment
  • Patients who who are, in the opinion of the investigator, known to be unreliable or non-compliant with medical treatment, or are known to miss appointments (according to patient records)
  • Patients who drug abuse problems, mental dysfunction or other factors limiting their ability to cooperate fully
  • Patients who any other condition or prior/present treatment which, in the opinion of the investigator, will render the patient ineligible for the study

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Pimecrolimus cream treatment
Comparateur actif: Betamethasone valerate cream treatment

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
To explore the effect of 1 % pimecrolimus cream on the epidermis in adults with AD

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. 1 % pimecrolimus cream leads to a reduction of biophysical parameters of AD representing the permeability barrier of the skin after three weeks of treatment.
  2. To explore the epidermal effect on proliferation rate, differentiation, and stratum corneum lipid content.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
To explore the effect of 1 % pimecrolimus cream induced changes in ultra-structure and gene expression in the epidermis
  1. To explore the effect of 1 % pimecrolimus cream induced changes in ultra-structure and gene expression in the epidermis.
  2. To compare the key protein molecules of keratinocyte growth and differentiation and their gene expression in relationship to clinical skin improvement.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Les enquêteurs

  • Chercheur principal: Ehrhardt Proksch, MD, PhD, Dept. of Dermatology, University of Kiel

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 mars 2005

Achèvement primaire

7 décembre 2022

Achèvement de l'étude

7 décembre 2022

Dates d'inscription aux études

Première soumission

26 mai 2010

Première soumission répondant aux critères de contrôle qualité

26 mai 2010

Première publication (Estimation)

27 mai 2010

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

27 mai 2010

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 mai 2010

Dernière vérification

1 mars 2005

Plus d'information

Termes liés à cette étude

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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