Clinical Research Directory

Tolerance Results and Immune Mechanisms in Cow´s Milk and/or Hen´s Egg Allergic Children Following Natural Evolution or Oral Immunotherapy

Allergy to Cow's milk and hen´s egg proteins are the most common causes of food allergies in early childhood and are associated with the occurrence of adverse events that may be life-threatening, quality of life impairment and negative nutritional and health economic impact. However, contrarily to other food allergy models such as nuts/peanut allergy, milk and egg allergy have greater chances of natural resolution. While around 50% of children may outgrow milk or egg allergy by the age of 5 years old, only 22% of peanut allergic children at the age of 4 years can tolerate this food. However, it is also documented that, at 14 years of age, the persistence of milk and egg allergy still affects around 30% of these children. Standard of care relies on food avoidance and treatment of accidental reactions, but this approach is unsatisfactory because adverse events and quality of life limitations still remain. Milk and egg Oral Immunotherapy (OIT) is the most promising therapeutic alternative and showed good results to induce Desensitization (ability to tolerate the food while it is regularly taken) but insufficient efficacy to achieve Sustained Unresponsiveness (SU) (ability to tolerate the food after a period of avoidance). In the day-to-day practice, families and allergists of milk and egg allergic children frequently face the following dilemma: what is the best approach? Keep waiting for natural resolution or embarking in OIT? At the moment, there are only very limited data to guide this decision, specially in children with mild to moderate allergy, that still after 6 years of age withhold relevant chances of naturally outgrowing their allergy. Our objective is conducting a longitudinal cohort-study of children undergoing food avoidance and children undergoing OIT to assess biomarkers of natural allergy resolution/persistence and OIT Desensitization/Sustained Unresponsiveness trajectories.

Comparison Between a Rush and a Conventional Oral Immunotherapy Protocol to Treat Cow's Milk and Hen´s Egg Allergy. CompITO Study

This study investigates the efficacy and safety of two different OIT schemes to treat milk and egg allergic children

Understanding the Immune System's Role in Tree Nut and Peanut Allergies: Key Biomarkers for Diagnosis and Treatment Monitoring and Treatment Targets

Peanut and tree nuts belong to the main elicitors of pediatric food allergy and are the main cause of near fatal reactions in children requiring emergency management. Oral immunotherapy has emerged as an alternative treatment option for the management of food allergies, to enhance patients' safety and quality of life. Monitoring if the therapy is working relies on oral food challenges during the course of treatment. There is a clear need for reliable biomarkers that are reflective of the clinical progression during oral food challenges and during immunotherapy that would help with patient stratification and possibly for personalized treatment approaches in the future The aim of this study is to measure immune parameters in the blood of nut-allergic participants during oral food challenges and during the course of oral immunotherapy. The main questions the study aims to answer are: 1. Identify immune markers that correlate with clinical reactivity 2. Identify immune changes and markers that correlate with immunotherapy outcome Researchers will compare these immune parameters between nut-allergic participants on oral immunotherapy and with nut-allergic participants on avoidance diet. Additionally, we will also compare the immune parameters of these nut-allergic participants with those healthy adults.

Determine Immunoglobulin G4 (IgG4) Standards for Cow's Milk and Egg in Different Populations of Allergic and Non-allergic Children

The study objectives are : Determine standards of plasma levels of casein-specific immunoglobulin G4 (IgG4) and egg-specific immunoglobulin G4 (IgG4) as a function of age, in non-allergic children, in allergic children, and in cured former allergic patients. Analyze the plasma IgG4 / IgE ratio, according to the result of the oral provocation test (tolerance versus allergy) and, in the event of a reaction, according to the reactogenic dose (dose which caused the reaction).Determine whether analysis of the plasma metabolome can identify children with a cured allergy to cow's milk protein or to egg from those with a persistent allergy.

Sustained Unresponsiveness (SU) to Cashew Nut Protein Following Oral Allergen-Specific Immunotherapy

This study is a long-term follow-up of participants from the randomized controlled trial (RCT) "Efficacy of Cashew Nut Protein Immunotherapy: A Protocol of a Single-Center Randomized Controlled Trial in the Pediatric Population", NCT06328504. At the end of the original RCT all participants will undergo an open Oral Food Challenge (OFC) to assess desensitization after 3 months on the maintenance dose of OIT. Patients who have completed the first part of the study will be invited to the current part of the project: * First arm (initial experimental group) - patients will continue oral immunotherapy (OIT) with cashew nut protein (1200mg) for the next 8 months (+/- 3 weeks). * Second arm (initial control group - one year on a cashew nut elimination diet) - patients will begin OIT following the protocol used in the first part of the study (RCT). Upon completion of this initial phase, they will continue immunotherapy for an additional 8 months (+/- 3 weeks). After an additional 8 months (+/- 3 weeks) of OIT, all study participants will undergo a 4-week cessation of treatment, followed by an open Oral Food Challenge (OFC) to assess the development of sustained unresponsiveness (SU).

The Role of NIchel and LTPs Sensitization in Functional Gastrointestinal Disorders: the NILT Study

Non-specific lipid transfer proteins (nsLTPs) are currently recognized as the most prevalent cause of primary IgE-mediated food allergy in Mediterranean populations and constitute a leading trigger of anaphylactic reactions. In Italy, the prevalence of LTP sensitization is estimated at 2-2.4% in adults and approximately 9% in children, with marked geographic variation. Specifically, higher prevalence rates are observed in central and southern regions and on the islands (21.3%-27.2%) compared to the northern regions (approximately 11%). LTPs are ubiquitous panallergens, widely expressed throughout the plant kingdom. They represent the major allergens within the Rosaceae family in individuals not sensitized to birch pollen and have also been identified and characterized in numerous plant-derived foods, including nuts, legumes, rice, maize, beer, spelt, and wheat. The clinical spectrum of LTP hypersensitivity is highly heterogeneous. While a significant proportion of sensitized individuals remain asymptomatic, others may present with localized reactions such as contact urticaria or oral allergy syndrome (OAS). More severe cases may involve gastrointestinal symptoms (e.g., vomiting, epigastric discomfort, abdominal pain), cutaneous and respiratory manifestations, and systemic responses up to anaphylactic shock. Nickel is a ubiquitous metal employed in a wide range of industrial applications and consumer products, including stainless steel, metal plating, various alloys, and inexpensive jewelry. It is also naturally present in both animal and plant-based food sources (e.g., cereals, cocoa, legumes, fresh fruits and nuts, fish). Nickel is the most common sensitizer in allergic contact dermatitis, affecting approximately 20% of the general population and around 10% of the pediatric population. Sensitization to nickel involves a delayed-type (Type IV) hypersensitivity reaction and is not IgE-mediated. Clinical manifestations range from localized allergic contact dermatitis to systemic involvement, referred to as systemic nickel allergy syndrome (SNAS), which is characterized predominantly by gastrointestinal symptoms, although respiratory and other systemic manifestations can also occur. Gastrointestinal symptoms such as gastroesophageal reflux disease (GERD), functional dyspepsia, abdominal pain, and altered bowel habits, when not associated with overt allergic signs or underlying organic disease, are typically classified as functional gastrointestinal disorders (FGIDs). Several studies report that up to 40% of adult patients with FGIDs exhibit nickel sensitization; however, data in the pediatric population remain scarce. Chelanik® is a dietary supplement designed to support individuals with nickel hypersensitivity. It contains bioactive components purported to exert immunomodulatory and anti-inflammatory effects. Nevertheless, in vitro human data directly demonstrating its activity on lymphocyte function are currently lacking. This prospective, experimental, single-center study aims to determine the prevalence of sensitization to LTP and nickel among patients presenting with functional dyspepsia or irritable bowel syndrome (IBS), and to assess in vitro the potential immunomodulatory effects of Chelanik® on peripheral blood lymphocytes from individuals with nickel allergy.

Sustained Unresponsiveness (SU) to Sesame Protein Following Low-dose Oral Allergen-specific Immunotherapy

This study is a long-term follow-up of participants from the randomized controlled trial (RCT) "Efficacy and Safety of Low-Dose Sesame Oral Immunotherapy in Pediatric Patients", NCT06261554. At the end of the original RCT all participants will undergo an open Oral Food Challenge (OFC) to assess desensitization after 3 months on the maintenance dose of OIT. Patients who have completed the first part of the study will be invited to the current part of the project: * First arm (initial experimental group) - patients will continue oral immunotherapy (OIT) with low dose of sesame protein (300mg) for the next 8 months (+/- 3 weeks). * Second arm (initial control group - one year on a sesame elimination diet) - patients will begin OIT following the protocol used in the first part of the study (RCT). Upon completion of this initial phase, they will continue immunotherapy for an additional 8 months (+/- 3 weeks). After an additional 8 months (+/- 3 weeks) of OIT, all study participants will undergo a 4-week cessation of treatment, followed by an open Oral Food Challenge (OFC) to assess the development of sustained unresponsiveness (SU).

Evaluation of The Food Allergy Mastery Program

The proposed research project will evaluate a novel behavioral intervention that promotes early adolescent food allergy self-management and adjustment through 1) food allergy education, 2) problem-solving, communication, assertiveness, and anxiety management skill building, and 3) peer support.

Improving Diagnosis of Legume Allergy in Children

In France, almost 15% of serious food allergies in children are caused by legumes, especially peanuts. Other legumes like soy, lentils, peas, lupin, chickpeas, beans, and fenugreek can also cause allergic reactions. But here's the problem: only peanuts, soy, and lupin are required to be clearly labeled on food packaging in the European Union. This makes it hard for families to know when other legumes-like peas or fenugreek-are hidden in processed foods. Avoiding all these legumes is hard-especially since many of them are used in processed foods and not always listed on the label. Right now, detailed allergy tests to evaluate the probability of allergy diagnosis are only available for peanuts and soy, and not for other legumes. LACID study has been created to find and study the proteins in lupin, fenugreek, and peas that may cause allergies and developp better allergy tests for these legumes-possibly as part of a diagnostic tool that can give clear results using just a blood sample. The goal is to help doctors and families better understand which legumes a child really needs to avoid-and which ones are actually safe to eat.

Effect of Omalizumab in the Skin of Food Allergy Patients

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.

Boiled Tree Nut for Oral Immunotherapy in Food-allergic Children

As the global prevalence of food allergy steadily increases, tree nut (TN) becomes one of the main triggers of food-allergic reactions and food anaphylaxis. Since there is no effective cure, TN-allergic patients and their families must continue to live with this chronic, disabling condition while avoiding allergens and responding to allergic reactions with emergency treatment. An emerging experimental treatment for food allergy is oral immunotherapy (OIT). Tree nut OIT appears promising in preliminary studies but there are concerns about the high risk of adverse reactions to TNs used in the treatment. The rate of remission with TN OIT is also lacking. Identification of OIT regimes with increased efficacy and safety is urgently needed. The investigators revealed that boiled cashews had lower allergenic potential but retained mast cell reactivity. The aim of this proposed study is to investigate the efficacy and safety of a novel treatment strategy for TN-allergic individuals, whereby the investigators hypothesized that consuming increasing quantities of boiled cashews can induce desensitization/ remission to roasted tree nuts in children with cashew allergies.

Fish Oral Immunotherapy in Hong Kong Children

At present there is no cure for food allergy. People with a food allergy need to avoid the food they are allergic to in order to stay safe, but we know that accidental exposure is common. Researchers have begun to look at the effectiveness of 'oral immunotherapy' as a treatment for food allergy but results have been mixed. This study is a randomized controlled trial to evaluate the effectiveness of Fish Immunotherapy (FOIT), with codfish as the primary focus, in inducing tolerance in children with fish allergy compared with Placebo. Children will take increasing doses of codfish protein until a total of 12 months treatment is completed. Children will be tested for fish allergy at the start of the study, at the end of fish treatment T1 (12 months) and T2 (8 weeks) after treatment.

The Significance of a Timely Food Allergy Diagnosis and Optimal Surveillance of Nutritional Status in Children

The aim of this study is to gain more knowledge on the nutritional and immunological aspects of allergy to milk and eggs in children.

Preventing Atopic Dermatitis and ALLergies in Children

The primary objective is of the PreventADALL study is to test if primary prevention of allergic diseases is possible by simple and low cost strategies, and secondary to asses the impact of xenobiotic exposure and microbiota in and on the body and the environment on allergic disease development. The secondary objective is an exploratory focus to investigate early life risk factors for development of non-communicable diseases, including asthma and allergic diseases as well as for diseases that may share common risk factors, including cardiovascular disease, obesity and diabetes. Design: A multi-national population-based prospective birth cohort with a factorial designed randomized controlled intervention trial of two clinical interventions; skin care 0-9 months and early food introduction by 3-4 months, thereafter observation only. Recruitment in three cities (Oslo, Ostfold and Stockholm) of approximately 2500 mother-child pairs is done in two steps; first pregnant women are recruited and enrolled at the 18-weeks ultrasound investigation (n=approximately 2700) and thereafter their new-born babies are included. Randomization into four groups is done by the postal code or "township" to ensure all four intervention-groups within each "township". Visits for biological and environmental sampling, observations and investigations will be at the relevant pediatric departments (at 3-6-12-24-36 months of age) and through childhood into adulthood thereafter, provided sufficient funding.