Clinical trial NCT01782703: Defining the Skin and Blood Biomarkers of Pediatric Atopic Dermatitis
Official title: Defining the Skin and Blood Biomarkers of Pediatric Atopic Dermatitis SUB-STUDY: Defining the Predictive Non-Invasive Biomarkers for Pediatric Atopic Dermatitis (Funded by Regeneron Pharmaceuticals, Inc.)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Atopic Dermatitis
Eczema
Keywords: Atopic Dermatitis
Filaggrin
Biomarkers
Eczema
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Rockefeller University
name: Icahn School of Medicine at Mount Sinai
First posted: 2013-02-04
Enrollment: 505
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be recruited at Ann and Robert H. Lurie Children's Hospital Dermatology outpatient clinics.

* 200 children with mild to severe AD, 100 aged-matched and sex-matched healthy (no evidence of atopy) controls, 100 aged-matched and sex-matched controls with an atopic condition (allergic rhinitis or asthma) but no history of atopic dermatitis
* AD subjects between the ages of 0 months to 4 years of age will be asked to give buccal (cheek) swabs
* 70 children with mild to severe atopic dermatitis, and 70 age- and sex-matched (but not site-matched) healthy controls (no evidence of atopy), will be enrolled to obtain skin biopsies.
* 30 children with atopic dermatitis and 30 age/sex matched non-atopic controls for imaging evaluation.
* Transepidermal water loss values will obtained in 300 healthy controls.
* Cord blood will be collected from 30 healthy subjects at the time of delivery.

Brief summary: Atopic dermatitis (AD), also known as eczema, is the most common inflammatory skin disorder of children, affecting 10-20% of children and 1-2% of adults.

This skin disorder can be associated with unbearable itchiness and an increased susceptibility to skin infections. The cause of AD is currently poorly understood; therefore, there are no targeted treatment options at present. There have been recent studies in adults with AD that explain the cause and give us new routes to investigate treatment options, however no major studies in this arena have been done in children. We hope to evaluate the skin and blood biomarkers that are found in pediatric AD and compare them to adult AD.

Hypothesis: The immune system worsens the skin barrier issues that are common in atopic dermatitis. We believe there are similar immune and skin abnormalities in adult versus pediatric atopic dermatitis. Finally, blood levels of the activated molecules in atopic dermatitis can serve as surrogates for skin immune activation and will correlate with disease severity.

Detailed description: Objectives:

1. To define the cellular and molecular biomarkers of atopic dermatitis in skin biopsies and blood samples from a pre-adolescent pediatric population and correlate it with disease severity.
2. To measure the skin barrier in atopic dermatitis.
3. To determine quality of life in atopic dermatitis through various questionnaires.

Objectives for the non-invasive biomarkers sub-study:

1. Develop a panel of non-invasive biomarkers in tape strips and serum.
2. Correlate mRNA expression from tape-striped skin with individual markers of severity (EASI, SCORAD, pruritus and TEWL).
3. Correlate mRNA markers in blood with severity scores.
4. Correlate serum protein markers with severity scores.
5. Compare biomarkers based on patient age.
6. Correlate the biomarker candidates from tape strips and blood with the "gold standard" set of biomarkers derived from age-matched skin biopsy samples

Eligibility criteria: Inclusion Criteria:

* Subjects may be of either sex and must be between the ages of 0 months and 17 years at the time of enrollment (Healthy controls, atopic controls, and AD patients)
* The skin sample and blood sample for healthy controls can have no systemic inflammatory disease or personal or familial history of atopy (hives, food allergy, allergic rhinitis or conjunctivitis, asthma)
* The atopic blood sample controls may have an atopic condition (allergic rhinitis or asthma) but no history of atopic dermatitis
* All controls for skin sampling may have no observable abnormality in the sampled skin and, to further assure the normality of the "normal" skin edges, must not have evidence of inflammation or epidermal change in the lesion to be surgically removed
* AD subjects must have mild to severe atopic dermatitis with either new onset disease within the last 6 months or with acute exacerbation of AD
* Subjects 17 years of age and older and parents/guardians of minors must sign the approved IRB assent and consent form(s) respectively prior to initiation of the study protocol

Exclusion Criteria:

* Subjects unable to give assent or parents unable to give consent due to cognitive delay or inability to understand the assent form either in writing or presented verbally (Healthy controls, atopic controls, and AD patients)
* All subjects whose main diagnosis is deemed unsafe by the study investigator for study participation. Examples include known hemophilia or other blood disorders, or skin infection at the site of blood draw or biopsy (Healthy controls, atopic controls, and AD patients)
* Control subjects with obvious xerosis (Healthy controls and atopic controls)

Primary outcomes:
measure: Cellular infiltrates
timeFrame: One year
measure: Gene expression
timeFrame: One Year
Secondary outcomes:
measure: Correlation of biomarkers to quality of life
timeFrame: One year
Other outcomes:
measure: Development of a panel of non-invasive biomarkers from tape strip samples
timeFrame: Two years
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Northbrook
country: United States
facility: Northbrook Lurie Children's Outpatient Clinic
state: Illinois
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Northwestern University
name: Amy Paller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Emma Guttman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bieber T. Atopic dermatitis. Ann Dermatol. 2010 May;22(2):125-37. doi: 10.5021/ad.2010.22.2.125. Epub 2010 May 17.
citation: Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis--part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011 Jun;127(6):1420-32. doi: 10.1016/j.jaci.2011.01.054. Epub 2011 Mar 21.
citation: Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis--part I: clinical and pathologic concepts. J Allergy Clin Immunol. 2011 May;127(5):1110-8. doi: 10.1016/j.jaci.2011.01.053. Epub 2011 Mar 8.