ADRN Barrier/Immunoprofiling Exploratory Pilot Study

Completed

• Conditions: Dermatitis; Eczema; Non-atopic Healthy Controls; Dermatitis, Atopic

• Registration Number: NCT02115399
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

The purpose of this study is to look at how defects in the skin barrier and immune response affect risk for skin infections.

Participants will be classified into 4 groups based on Atopic Dermatitis (AD)/Non-Atopic (NA) status and Staphylococcus aureus (S. aureus) colonization (negative or positive):

* AD S. aureus negative

* AD S. aureus positive

* NA S. aureus negative and

* NA S. aureus positive.

Detailed Description

Atopic dermatitis, also called eczema, is a disease in which the skin is dry and scaly with severe itching. People with atopic dermatitis have defects in the skin barrier as well as defects in the immune system which fights off skin infections. People who have atopic dermatitis often have complications from viral and bacterial skin infections, such as recurring Staphylococcus aureus (S. aureus), or Staph infections.

The study will compare the skin barrier and immune response of people with and without atopic dermatitis in relation to whether Staph bacteria is growing on their skin.

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-14
• Study First Submitted QC: 2014-04-15
• Study First Posted: 2014-04-16
• Primary Completion: 2015-03
• Study Completion: 2015-06
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-23
• Last Update Posted: 2015-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Participants fulfilling all of the following criteria are eligible for enrollment-

• Non-Hispanic Caucasian males and females 18 to 60 years of age, inclusive, at the time of Enrollment
• Who are enrolled in the ADRN Registry study
• Who have active AD (lesions present) with or without a history of Eczema Herpeticum (EH) as defined in the ADRN Standard Diagnostic Criteria OR who meet criteria for the NA diagnostic group as defined in the ADRN Standard Diagnostic Criteria
• Who are willing to sign the informed consent form prior to initiation of any study procedures.

Exclusion Criteria

Participants fulfilling any of the following criteria are not eligible for enrollment-

• Who are pregnant
• Who have an active systemic malignancy. Uncomplicated non-melanoma skin cancer and melanoma in situ with documentation of complete excision are not exclusionary
• Who have any skin disease other than AD that might compromise the SC barrier (e.g., bullous disease, psoriasis, cutaneous T cell lymphoma [also called Mycosis Fungoides or Sezary syndrome], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease)
• Who have a history of systemic immunological illness (e.g., human immunodeficiency virus [HIV] or systemic lupus erythematosus [SLE]) other than the condition being studied
• Who have active EH or eczema vaccinatum (EV)
• Who have a history of serious or life-threatening reaction to latex, tape, or adhesives
• Who are determined to be not eligible based on the opinion of the Investigator.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The area under the transepidermal water loss (TEWL) curve	6 month	TEWL will be assessed using the AquaFlux AF200 (Biox, London UK) Transepidermal water loss (TEWL) will be assessed on non-lesional skin prior to tape stripping and repeated after 5, 10, 15, and 20 tape strips

Secondary Outcome Measures

Name	Time	Method
Basal transepidermal water loss (TEWL)	6 month	TEWL will be assessed using the AquaFlux AF200 (Biox, London UK)
Transepidermal water loss (TEWL) measured after 20 tape strips	6 month	Transepidermal water loss (TEWL) will be assessed using the AquaFlux AF200 (Biox, London UK). TEWL assessments will be done on non-lesional skin prior to tape stripping and after 20 tape strips and on unstripped lesional skin.
Change in transepidermal water loss (TEWL)	6 month	Transepidermal water loss (TEWL) will be assessed using the AquaFlux AF200 (Biox, London UK).; TEWL after 20 tape strips minus transepidermal water loss (TEWL) prior to tape stripping.
Change in transepidermal water loss (TEWL) per every 5 tape strips (i.e. slope)	6 month	TEWL will be assessed using the AquaFlux AF200 (Biox, London UK)
Quality of Life (QoL) measurement	6 month	Standardized questionnaires will be used to collect information regarding Quality of Life
Stratum Corneum (SC) hydration (capacitance)	6 month	Stratum Corneum(SC) hydration will be assessed on lesional and non-lesional skin using the Corneometer® CM825
Itch assessment	6 month	Standardized questionnaires will be used to collect information regarding contact itch intensity
Permeability assessment from skin biopsies	6 month	Two punch biopsies of non-lesional skin will be obtained. One biopsy will be used for assessments of Tight Junction (TJ) function including confocal imaging, Transepithelial Electrical Resistance (TEER), and permeability measurements.
Confocal staining of Tight Junction (TJs) from skin biopsies	6 month	Two punch biopsies of non-lesional skin will be obtained. One biopsy will be used for confocal staining of Tight Junction (TJs) and routine histology.
Analysis of S. aureus isolates for expression of virulence or other factors	6 month
Surface pH	6 month	Surface pH will be assessed on lesional and non-lesional skin using the Skin-pH Meter® PH 905
Stratum Corneum (SC) cohesion assessed as total protein removed per D-Squame tape	6 month	The assessment of SC cohesion will be conducted by two different methods. First, serial measurements of transepidermal water loss (TEWL) will be performed after tape stripping. Second, the amount of protein removed per strip will be calculated by an optical absorbance technique using a CuDerm SquameScan 850A.
Peripheral blood mononuclear cells (PBMC) expression of cell surface and intracellular markers	6 month	Measured after ex vivo stimulation with a polyclonal T cell stimulus, toll-like receptor ligands (TLRs), iron-regulated surface determinant B (IsdB) as an immunodominant S. aureus antigen, and recall antigens, such as influenza and tetanus antigens, and media alone as the control.
Transepithelial Electrical Resistance (TEER) assessment from skin biopsies	6 month	Two punch biopsies of non-lesional skin will be obtained. One biopsy will be used for assessments of Tight Junction (TJ) function including confocal imaging, Transepithelial Electrical Resistance (TEER), and permeability measurements
Atopic Dermatitis (AD) severity assessments	6 month	AD severity assessments include the Eczema Area and Severity Index (EASI), Rajka-Langeland (R-L) score, and Investigator Global Assessment (IGA)
Analysis of S. aureus isolates for antibiotic sensitivity	6 month	Antibiotic resistance is characterized by methicillin sensitive Staphylococcus aureus (MSSA) vs. methicillin resistant Staphylococcus aureus (MRSA)

Trial Locations

Locations (3)

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Rochester; 🇺🇸 Rochester, New York, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States