Clinical trial NCT03168113: Atopic Dermatitis (AD) and Food Allergy
Official title: Skin Barrier in Childhood Atopic Dermatitis With and Without Food Allergy (ADRN-10)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atopic Dermatitis (AD)
Non-atopic Healthy Controls
Keywords: skin barrier function
microbiome
transepidermal water loss (TEWL)
epidermal transcriptome
epidermal lipid composition
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Atopic Dermatitis Research Network
First posted: 2017-05-30
Enrollment: 62
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children ages 4-17 years, inclusive. Enrollment will include 20 AD children with food allergy to peanut, 20 AD children without a history of food allergy, and up to 20 NA children. The study requires that AD participants with peanut allergy meet the 95% positive predictive value for skin prick test (≥ 8 mm wheal) for peanut allergy. Food allergic AD participants will be allowed to have other food allergies in addition to peanut. A subset of children with AD whose disease is too severe to stop prohibited medications as defined in the protocol will be excluded. NA children will serve as a healthy control group for the AD study participants. Enrollment is to children since AD and food allergies are more prevalent among children, and adult onset AD and/or food allergy is a different phenotype.

Brief summary: This is a prospective, single center, clinical mechanistic pilot clinical research study. Participants will not receive any investigational agent. The investigators will examine whether children with atopic dermatitis (AD) and food allergy have a different skin barrier, microbiome, epidermal transcriptome, and epidermal lipid composition than children with AD and no food allergy and non-atopic (NA) children. Participation involves a single study visit.

Detailed description: Atopic Dermatitis (AD) is a chronic inflammatory skin disorder in which the skin becomes extremely itchy and is susceptible to recurrent skin infections. AD is thought to occur from a combination of immunological, genetic, and environmental factors.

Those with atopic dermatitis (AD) often have food allergy and Staphylococcus aureus (S. aureus) colonization of the skin. There is evidence suggesting that skin barrier dysfunction, measurable as increased transepidermal water loss (TEWL), is a predisposing factor to food sensitization and food allergy from epicutaneous penetration of environmental food allergens. Furthermore, the investigators for this study have identified that AD children with food allergy, especially peanut allergy, are colonized with Staphylococcus aureus. However, only half (50%) of children with AD have food allergy or S. aureus colonization, suggesting there are other factors accounting for food allergy. There have been no previous studies of TEWL or, microbial or molecular profiling of the skin in those with AD prone to food allergy versus AD without food allergy.

Eligibility criteria: Inclusion Criteria:

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

-Parent/guardian must be able to understand and provide informed consent and participant provide assent as applicable per Institutional Review Board (IRB) guidelines and regulations;

For Eligibility to One of the Two Active Atopic Dermatitis (AD) Groups:

-Active Atopic Dermatitis (AD) without a history or current manifestations of eczema herpeticum (EH), as diagnosed using the Atopic Dermatitis Registry

Network (ADRN) Standard Diagnostic Criteria and food allergy to peanut. Participant must meet all of the following criteria:

* Self-report or documentation of a positive oral food challenge to peanut or self-report of an allergic reaction to peanut within 2 hours of ingestion
* Peanut skin prick test wheal ≥ 8 mm. OR -Active AD without a history or current manifestations of EH, as diagnosed using ADRN Standard Diagnostic Criteria and no food allergy.

Participant must meet all of the following criteria:

* No personal history or current manifestations of food allergy (based on no self-report of a positive oral food challenge, positive skin test, positive blood test, or allergic reactions).
* Negative skin prick test (wheal \< 3 mm) to peanut, milk, egg, wheat, soy, shellfish mix, tree nuts, and sesame seed.

For Non-atopic (NA) Group Eligibility:

Participant must meet all of the following criteria:

* No personal history or current manifestations of AD, asthma, or allergic rhinitis (based on self-report);
* No personal history or current manifestations of food allergy (based on no self- report of a positive oral food challenge, positive skin test, positive blood test, or allergic reactions);
* Negative skin prick test (wheal \< 3 mm) to peanut, milk, egg, wheat, soy, shellfish mix, tree nuts, and sesame seed; and
* Negative skin prick test (wheal \< 3 mm) to environmental allergens (cat, dog, dust mite, cockroach, and local trees/grasses/weeds/molds).

Exclusion Criteria:

* Inability or unwillingness of a parent/guardian to give written informed consent, or participant to give assent, if applicable, or to comply with study protocol;
* Subjects with skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous diseases, psoriasis, cutaneous T cell lymphoma \[also called Mycosis Fungoides or Sezary syndrome\], dermatitis herpetiformis, Hailey- Hailey, or Darier's disease);
* Pregnant or lactating females;
* Known or suspected immunosuppression;
* Severe concomitant illness(es);
* History of serious life-threatening reaction to latex, tape, or adhesives;
* Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study;
* Use of biologics within 5 half-lives (if known) or 16 weeks of the Screening Visit;
* Use of an investigational drug within 5 half-lives (if known) or 8 weeks of the Screening Visit; or
* Has received immunotherapy within 12 months of the Screening Visit.

Primary outcomes:
measure: The Transepidermal Water Loss (TEWL) Area Under the Curve
timeFrame: Visit 1 (Day 1)
Secondary outcomes:
measure: Basal Transepidermal Water Loss (TEWL)
timeFrame: Visit 1 (Day 1)
measure: Transepidermal Water Loss (TEWL) Measured After 20 Tape Strips
timeFrame: Visit 1 (Day 1)
measure: Lipid Profiles
timeFrame: Visit 1 (Day 1)
Other outcomes:
measure: EXPLORATORY: Protein Expression Profiles
timeFrame: Visit 1 (Day 1)
measure: EXPLORATORY: Gene Expression Profiles
timeFrame: Visit 1 (Day 1)
measure: EXPLORATORY: Microbial Carriage
timeFrame: Visit 1 (Day 1)
measure: EXPLORATORY:Carriage of Transcriptionally Active Microbial Species
timeFrame: Visit 1 (Day 1)
measure: EXPLORATORY: Frequency of Commensal Antimicrobial Coagulase-Negative Staphylococcus (CoNS)
timeFrame: Visit 1 (Day 1)
Locations:
city: Denver
country: United States
facility: National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
state: Colorado
Study officials:
affiliation: National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
name: Donald Leung, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lyubchenko T, Collins HK, Goleva E, Leung DYM. Skin tape sampling technique identifies proinflammatory cytokines in atopic dermatitis skin. Ann Allergy Asthma Immunol. 2021 Jan;126(1):46-53.e2. doi: 10.1016/j.anai.2020.08.397. Epub 2020 Sep 5.