The goal of this interventional study is to evaluate whether skin barrier abnormalities occur in subjects with a food allergy, as determined by positive oral food challenge (OFC). The main question it aims to answer is whether these skin barrier abnormalities can be reversed by omalizumab. If there is a comparison group: Researchers will compare non-food allergic participants (who do not receive omalizumab) to see if they experience skin barrier abnormalities. All food allergic participants will receive 4 months of Omalizumab treatment as well as two Oral Food Challenges. Participants will all undergo skin barrier assessments.
This is a phase IV open-label interventional pilot study of 30 patients enrolled at National Jewish Health to examine skin barrier function and response to OFC in patients with FA before and after 4 months of treatment with omalizumab. If enrollment is insufficient at National Jewish, Children's Hospital Colorado or another similarly qualified site will be used as a back-up site. Efficacy assessment will be assessed by the ability of Omalizumab to reduce clinical response to OFC. The safety of omalizumab will be concomitantly recorded. Specifically, we will: 1. Examine TEWL, STS lipidomics, metabolomics, cytokines, and proteomics in 30 patients with a history of IgE-mediated reaction to 1 or more foods assessed by sensitization food extracts using skin prick tests, serum IgE to specific foods and/or relevant component proteins, and an IgE-mediated clinical reaction to a food on OFC. 2. Confirm the diagnosis of IgE-mediated FA in all patients with a positive OFC. 3. Treat all 30 patients with omalizumab for 4 months 4. Repeat OFC after 4 months of omalizumab therapy. 5. To analyze TEWL, STS Lipidomics, metabolomics, proteomics, and cytokines in all 30 patients who were treated with omalizumab and completed the end of study OFC. Sample size will be 30 completed subjects. Enrollment will occur over the course of 16 months, with 2-4 participants enrolling each month. Up to ten healthy control subjects will also be enrolled for skin tape strip analysis and TEWL as a comparator group to the FA group. All participants will have an initial screening visit where their clinical history of having an IgE-mediated reaction to specified food(s) will be elucidated, along with review of relevant skin prick test (SPT), food-specific IgE values, and Total IgE. If these values were not obtained within the last 12 months, SPT, sIgE, and/or Total IgE will be performed at screening. All food-allergic participants will undergo an open Screening OFC to one of their food allergens. For continuation in the study, the participant must experience dose-limiting symptoms consistent with an IgE-mediated reaction, at or before 444mg of food protein cumulatively. If they have a negative OFC, additional screening OFCs may be performed to any eligible food. STS and TEWL measurements will be performed prior to the first dose, as well as before the second and third doses. If/when the participant has dose-limiting symptoms, STS and TEWL will be stopped immediately. All food-allergic participants will receive omalizumab for 4 months. All injections will be administered by a research nurse on the clinical research unit. At the midway point of the study (2 months after the first omalizumab injection), the participant will have STS and TEWL measurements performed. After 4 months of omalizumab administration, an end of study OFC will be performed to the same food that was positive at the screening OFC to assess treatment effect, along with analysis of the STS and TEWL.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
Omalizumab is a monoclonal antibody FDA-approved for treatment of food allergy.
National Jewish Health
Denver, Colorado, United States
RECRUITINGLipidomic analysis
Lipid measurements from Skin Tape Strips (STS), as detected at respective m/z from mass spectrometry
Time frame: 5 months
Metabolomic analysis
Metabolomics from STS, evaluated as a relative signal proportion of metabolites against the sum of all signals in the samples
Time frame: 5 months
Proteomic analysis
Proteomics from STS, comparison of global protein expression before vs after omalizumab treatment
Time frame: 5 months
Cytokine analysis
Cytokine levels from STS measured using preconfigured multiplex assays normalized to the total protein in each sample. Cytokines that will be measured: IL-1a, IL-1b, IL-18, IL-6, IL-8, TARC, MDC, TSLP, IL-33, IL-4, IL-13, IL-22, IL-31, eotaxins, IL-10, IL-17A/F, IL-17C, IL-12p70, IL-23, IP-10
Time frame: 5 months
Measurement of Transepidermal Water Loss
Transepidermal Water Loss (TEWL) is measured by the loss through the skin of grams of water per square meter per hour (g/m\^2/h).
Time frame: 5 months
Measurement of Transepidermal Water Loss in non Food-Allergic Subjects
Transepidermal Water Loss (TEWL), grams water per square meter per hour (g/m\^2/h)
Time frame: 5 months
Lipidomic analysis in non Food-Allergic participants
Lipid measurements from Skin Tape Strips (STS), as detected at respective m/z from mass spectrometry
Time frame: 5 months
Metabolomic analysis in non Food-Allergic Participants
Metabolomics from STS, evaluated as a relative signal proportion of metabolites against the sum of all signals in the samples
Time frame: 5 months
Proteomic analysis in non Food-Allergic Participants
Proteomics from STS, baseline expression levels of proteins found in non-allergic skin tapes.
Time frame: 5 months
Cytokine analysis
Cytokine levels from STS from non-Food Allergic participants, measured using preconfigured multiplex assays normalized to the total protein in each sample. Cytokines that will be measured: IL-1a, IL-1b, IL-18, IL-6, IL-8, TARC, MDC, TSLP, IL-33, IL-4, IL-13, IL-22, IL-31, eotaxins, IL-10, IL-17A/F, IL-17C, IL-12p70, IL-23, IP-10
Time frame: 5 months
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