Clinical trial NCT04198753: Skin Characteristics of Parents of Food Allergic Pediatric Patients
Official title: Skin Characteristics of Parents of Food Allergic Pediatric Patients
Study type: OBSERVATIONAL
Overall status: SUSPENDED
Conditions: Food Allergy in Children
Lead sponsor: National Jewish Health
Sponsor class: OTHER
First posted: 2019-12-13
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Peanut allergic patients/subjects will be identified via the NJH EMR or database. Parents may be approached by listed study staff at the beginning or end of their scheduled NJH visit and asked about their food allergy history and interest in enrollment. Alternatively, this may be done over the phone. Thereafter, eligibility will be determined using the listed inclusion and exclusion criteria.

Brief summary: The purpose of this study is to determine whether disruptions in the skin barrier of parents can contribute to the development of food allergies in their offspring. The study team will compare the superficial skin layers of mothers and fathers who do not have children with diagnosed food allergies to the skin layers of parents who do have children with diagnosed food allergy. The study will include a questionnaire, noninvasive superficial skin testing with skin tapping and transepidermal water loss measurements, and a blood draw.

Detailed description: There is an already well-established link between atopic dermatitis (AD), or eczema, and the development of food allergies. More specifically, it is believed that sensitizations to food can occur through low-dose cutaneous sensitization via a disrupted skin barrier. The strongest genetic contributor to eczema is the FLG loss-of-function or missense mutation, which is associated with increased transepidermal water loss and increased skin permeability (1). In a recent study exploring the risk of maternal transmission of allergic risk, it was found that children of FLG-carrier mothers had a 1.5 increased AD risk, specifically when these mothers had allergic sensitization (elevated allergen-specific IgE antibody plasma levels) but independent of their own FLG mutation status (10). This information may suggest that an interrupted skin barrier in mothers may serve as an environmental risk factor for the development of food allergies in their offspring.

The purpose of our study is to evaluate the skin characteristics and FLG gene mutation status of parents of known food allergic pediatric patients. The researchers hypothesize that parents of food allergic patients will have more significant disruptions in their skin barrier function than parents of children who do not suffer from food allergies.

In order to evaluate skin barrier disruptions in these subjects, two noninvasive methods will be performed including skin tape stripping, a total of 30 strips per subject, and transepidermal water loss measurements using a small device. Both methods are relatively painless and cause minimal risk to the participant. In order to evaluated FLG gene mutation status, blood draw will also be performed. Subjects will undergo a focused physical exam and also be requested to fill out a detailed questionnaire. The researchers will obtain additional offspring peanut allergy clinical characteristics from the medical records. All data collection will occur over 1-2 visits, averaging an anticipated 1 hour in total duration.

Eligibility criteria: Inclusion Criteria:

1. Subject has signed the informed consent form
2. 18 years of age or older (inclusive) 3. One of the following Diagnostic Categories:

   1. Normal healthy controls with no personal or offspring history of food allergy or atopic dermatitis
   2. Mother or father without personal history of food allergy, but with a child diagnosed with peanut allergy. Peanut allergy is defined as fulfilling one of the following 3 criteria:

   i. Clinical history defined as one of the following occurring within 2 hours of exposure to peanut:
   1. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)
   2. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
   3. Reduced BP or associated symptoms (eg, hypotonia \[collapse\], syncope, incontinence)
   4. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting)

ii. Positive skin prick testing \> 8 mm

iii. Positive specific IgE to peanut \> 14.0 kUA/L

Exclusion Criteria:

1. Has active flare of atopic dermatitis requiring use of bleach baths, topical corticosteroids, topical immunomodulatory agents, or topical antibiotics on the extremity being evaluated
2. Has a skin disease other than AD that might compromise the stratum corneum barrier such as bullous disease, psoriasis, cutaneous T cell lymphoma, Darier's disease, HaileyHailey, or dermatitis herpetiformis
3. Has a current systemic infection requiring use of systemic antibiotics, antiparasitics, antivirals, or antifungals
4. Has a severe concomitant disease or immunosuppression such as lymphoma, HIV, or Wiskott-Aldrich syndrome
5. Has a history of a severe reaction to latex, tape, or adhesives
6. Has used any biologics within 5 half-lives or 16 weeks, whichever is longer
7. Has received immunotherapy in the last 12 months
8. Has used any investigational drugs within 5 half-lives or 8 weeks, whichever is longer
9. Has used anticoagulants, anxiolytics, or antidepressants within 30 days
10. Has used of systemic immunosuppressive drugs including oral steroids within 30 days
11. Has received total body phototherapy (e.g., ultraviolet light B \[UVB\], psoralen plus ultraviolet light A \[PUVA\], tanning beds \[\>1 visit per week\]) within 30 days
12. Is pregnant or lactating (this will be self-verified by the patient)

Primary outcomes:
measure: Skin barrier dysfunction via skin tape stripping (STS)
timeFrame: 6-12 months
measure: Skin barrier dysfunction via transepidermal water loss (TEWL) measurements
timeFrame: 6-12 months
Secondary outcomes:
measure: FLG mutation status
timeFrame: 6-12 months
measure: Vitamin D status
timeFrame: 6-12 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
Study officials:
References:
citation: Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol. 2012 May;129(5):1187-97. doi: 10.1016/j.jaci.2012.02.036. Epub 2012 Mar 30.
citation: Esparza-Gordillo J, Matanovic A, Marenholz I, Bauerfeind A, Rohde K, Nemat K, Lee-Kirsch MA, Nordenskjold M, Winge MC, Keil T, Kruger R, Lau S, Beyer K, Kalb B, Niggemann B, Hubner N, Cordell HJ, Bradley M, Lee YA. Maternal filaggrin mutations increase the risk of atopic dermatitis in children: an effect independent of mutation inheritance. PLoS Genet. 2015 Mar 10;11(3):e1005076. doi: 10.1371/journal.pgen.1005076. eCollection 2015 Mar.
citation: Broccardo CJ, Mahaffey SB, Strand M, Reisdorph NA, Leung DY. Peeling off the layers: skin taping and a novel proteomics approach to study atopic dermatitis. J Allergy Clin Immunol. 2009 Nov;124(5):1113-5.e1-11. doi: 10.1016/j.jaci.2009.07.057. Epub 2009 Sep 12. No abstract available.
citation: Kelleher M, Dunn-Galvin A, Hourihane JO, Murray D, Campbell LE, McLean WHI, Irvine AD. Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year. J Allergy Clin Immunol. 2015 Apr;135(4):930-935.e1. doi: 10.1016/j.jaci.2014.12.013. Epub 2015 Jan 22.