Potential Role of AGEs in Paediatric Allergies

Allergy Clinical Trial

Official title:

The Potential Role of Advanced Glycation End-products in the Pathogenesis of Paediatric Allergies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04273152
• Other study ID #: 176/19
• Status: Completed
• Start date: January 1, 2018
• Est. completion date: March 30, 2020

Study information

• Verified date: October 2021
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Food allergy (FA) is "an adverse health effect arising from a specific immune response that occurs reproducibly" according to the 2010 National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH)-supported Guidelines for the Diagnosis and Management of Food Allergy in the United States (Boyce et al. 2010). Studies have suggested that the natural history of FA has changed during the last two decades, with a dramatic rise in the prevalence, severity of clinical manifestations, and risk of persistence into later ages, leading to an increase in hospital admissions, medical visits, treatments, and burden of care on families and to an important economic impact, with significant direct costs for the families and healthcare system (Skripak et al. 2007; McBride et al. 2012; Gupta et al. 2013). The development of FA might be influenced by genetics, environment, and genome-environment interactions, leading to immune system dysfunction, mediated at least in part by epigenetic mechanisms (Berni Canani et al. 2015; Paparo et al. 2018). Many factors have been postulated to contribute to the onset of FA. Among dietary factors, it has been hypothesized that advanced glycation endproducts (AGEs), present at high level in junk food, could be involved in FA pathogenesis. AGEs are a heterogeneous group of compounds deriving from a non-enzymatic reaction between reducing sugars and free amino groups of proteins, lipids, or nucleic acids. This reaction is also known as the Maillard or browning reaction. The formation of AGEs is a part of normal metabolism, but if excessively high levels of AGEs are reached in tissues and the circulation they can become pathogenic. AGEs are naturally present in uncooked animal-derived foods, and cooking results in the formation of new AGEs within these foods. Consumption of AGE-rich diets is associated with elevated circulating and tissue AGEs and an increase of their pro-inflammatory and pro-oxidant effects. On the other hand, restriction of AGEs prevents inflammation. AGEs not only exert their deleterious actions due to their biological properties, but also through their interaction with specific receptors (RAGE). AGEs are able to activate mast cells and induces a chronic inflammatory state that promotes a Th2 type response. The aim of this study is to evaluate the AGEs levels in FA children compared with healthy controls and subjects with other allergic diseases.

Description:

The study is designed to evaluate the AGEs concentration in allergic children compared with healthy controls and to investigate the potential role of AGEs in FA pathogenesis. First, the investigators will define subcutaneous AGEs levels in children affected by allergy, comparing to non-allergy children AGEs levels. Subsequently, the investigators will investigate the possible correlation with dietary habits and the potential effects of AGEs on gut barrier components and on non-immune and immune mechanisms in experimental models.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: March 30, 2020
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

Inclusion Criteria:

• Caucasian ethnicity

• Both sexes

• Age = 5 and =15 years with confirmed diagnosis of allergy (food and/or respiratory), and healthy controls age- and sex-matched.

Exclusion Criteria:

• Non caucasian ethnicity

• Age <5 or >15 years

• Concomitant presence of other chronic diseases not related to allergy (i.e., malignancy, immunodeficiency, cystic fibrosis, celiac disease, autoimmune diseases, neuropsychiatric diseases, diabetes mellitus type 1, chronic inflammatory bowel diseases, malformations of the urinary tract, gastrointestinal tract and/or respiratory tract, genetic-metabolic disorders, nervous system diseases, delayed psychomotor development, chronic lung diseases, hematological diseases)

• Presence of tattoos, scars, moles or lesions on both forearms

Related Conditions & MeSH terms

• Allergy
• Hypersensitivity

Intervention

Diagnostic Test:
• advanced glycation endproducts reader
advanced glycation endproducts reader

Locations

Country	Name	City	State
Italy	Pediatric Office	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The advanced glycation endproducts subcutaneous levels	the advanced glycation endproductssubcutaneous levels in allergic children compared with healthy controls.	at baseline
Secondary	the correlation between advanced glycation endproducts subcutaneous levels and dietary habits	the correlation between advanced glycation endproducts subcutaneous levels and dietary habits	at baseline
Secondary	the investigation of the potential pathogenetic role elicited by AGEs in allergy	Intestinal permeability (using transepithelial eletrical resistence), tight junction proteins expression (measured as fold change), the epithelial cell-derived danger signal mediators IL-33 and TSLP (pg/ml), RAGE pathway expression (measured as fold change), ROS production (expressed as optical density) analysis on human enterocytes cell line; IL-4, IL-5, IL-13, IL-10, IFN-g, IL-6, IL-8, TNF-a determination (pg/ml) on culture supernatants from peripheral blood mononuclear cells; Immunohistochemistry analysis of small intestinal biopsies (measured as number of CD25+ mononuclear cells)	at baseline