Pimecrolimus and Epidermal Barrier Function

NCT ID: NCT01132079

Last Updated: 2010-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31

Brief Summary

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.

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Pimecrolimus cream treatment

Group Type: EXPERIMENTAL

cream treatment

Intervention Type: DRUG

Betamethasone valerate cream treatment

Group Type: ACTIVE_COMPARATOR

cream treatment

Intervention Type: DRUG

Interventions

cream treatment

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsche Forschungsgemeinschaft, Bonn, Germany

UNKNOWN

Sponsor Role: collaborator

Novartis Pharma GmbH, Nürnberg, Germany

UNKNOWN

Sponsor Role: collaborator

University of Kiel

OTHER

Sponsor Role: lead

Responsible Party

Dept. of Dermatology, Venerology and Allergology, University Hospitals of Schleswig-Holstein, Campus Kiel, University of Kiel

Principal Investigators

Ehrhardt Proksch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Dermatology, University of Kiel

Locations

Dept. of Dermatology, University of Kiel

Kiel, , Germany

Countries

Germany

References

Jensen JM, Pfeiffer S, Witt M, Brautigam M, Neumann C, Weichenthal M, Schwarz T, Folster-Holst R, Proksch E. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol. 2009 May;123(5):1124-33. doi: 10.1016/j.jaci.2009.03.032.

Reference Type: RESULT

PMID: 19410693 (View on PubMed)

Jensen JM, Pfeiffer S, Witt M, Brautigam M, Neumann C, Weichenthal M, Schwarz T, Folster-Holst R, Proksch E. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol. 2009 Sep;124(3 Suppl 2):R19-28. doi: 10.1016/j.jaci.2009.07.015.

Reference Type: RESULT

PMID: 19720208 (View on PubMed)

Other Identifiers

Protocol No. ELBE-2005

Identifier Type: -

Identifier Source: org_study_id