Clinical Research Directory

Natural History and Genetics of Food Allergy and Related Conditions

Background: \- About 15 million Americans have a food allergy. Because there are no cures or effective prevention or treatment for food allergies, researchers want to learn more about them. Objective: \- To learn more about the causes and effects of food allergy and related conditions. Eligibility: * People ages 2 99 who have food allergy and/or a related genetic or other condition * Their relatives * Healthy relatives and volunteers Design: * Participants will have at least 3 visits over 1 2 years, and then once a year for up to 12 years. Each may last a day or longer. * Participants will be screened with medical history, physical exam, and questionnaires. * Participants may have the following: * Blood tests * Allergy skin prick tests: Drops of allergens are placed on the back or arm. The skin is scratched under each drop. * Leukapheresis: blood is taken from a needle in one arm, passed through a machine, and returned through a needle in the other arm. * X-rays * Esophageal string test: One end of a string is taped to the cheek and the other end is packed into a capsule. When the capsule is swallowed, the string unwinds; it is left in for at least 1 hour. * EGD and colonoscopy: Biopsies are taken from the gastrointestinal system. * Tiny biopsies of skin * Photographs of the body * Collection of cells through: * Swab of nose, inside of cheek, or skin * Gentle skin scrape * Tape stripping: piece of tape is put on the skin and pulled off.

PK/PD Study of IN-001 Sublingual Spray in Healthy Adults

This is an open-label, three-part study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine administered as a single dose of L-dipivefrin (IN-001) sublingual spray or drop in healthy adults. For all parts of the study, participants will undergo at least 10 hours of fasting prior to dosing. Part 1 of the study focuses on IN-001 dose/formulation exploration in a small number of participants (N=6); Part 2 of the study involving up to 12 participants will test a dose selected from Part 1 delivered as both a sublingual spray and a sublingual drop. In Part 3, one delivery method will be tested. Total number of participants is 30.

Environmental Exposure to Heavy Metals, Nanoparticles, and Emergent Contaminants and Risk of Allergic Diseases

The goal of this clinical trial is to collect environmental, bio-humoral, and clinical data derived from patients with allergic contact dermatitis (ACD) and systemic metal allergic syndromes related to the exposure to heavy metals, nanoparticles, and emergent contaminants and from healthy subjects. The main question it aims to answer is: are environmental, bio-humoral, and clinical data derived from patients with ACD and systemic metal allergic syndromes, related to the exposure to heavy metals, nanoparticles, and emergent contaminants, different from ones obtained by healthy subjects? Researchers will compare serum and urine concentration of heavy metals and nanoparticles, patch test to metals, within-breath analysis of oscillometry parameters, serum zonulin, and serum levels of protein oxidation products among patients with systemic allergic syndrome (1st study group), patients with ACD (2nd study group) and healthy subjects (3rd study group). Participants will undergo: * measurement of exposure to heavy metals and nanoparticles including nickel, cobalt, chromium, palladium, molybdenum, aluminium, and copper, through serum and urine measurement of concentration. * Patch test to before mentioned metals. * Within-breath analysis of oscillometry parameters. * Measurement of serum zonulin (related to gastro-intestinal exposure). * Measurement of serum levels of protein oxidation products (as markers of systemic oxidative stress).

Systems Biology of Early Atopy

The goal of this study is to establish a birth cohort that collects prenatal and early life biosamples and environmental samples and rigorously phenotypes young children for food allergy and Atopic Dermatitis (AD) to identify prenatal and early life markers of high risk for food allergy and AD, as well as biological pathways (endotypes) that result in these conditions. Primary Objectives: * To study the role and interrelationships of established and novel clinical, environmental, biological, and genetic prenatal and early-life factors in the development and course of allergic diseases through age 3 years (or 6 years for those who choose to continue participation into SUNBEAM II), with an emphasis on atopic dermatitis and food allergy * To apply systems biology to identify mechanisms and biomarkers underlying the development of food allergy, atopic dermatitis, and their endotypes * To collect, process, and assay or store environmental and biological samples for current and future use in the study of allergic disease development

Omalizumab Weight-Based Dosing Efficacy Trial

This research is being conducted to assess the safety and effectiveness of increased dosing of Omalizumab for food allergies.

Early Introduction and Sustained Ingestion (EISI) Using Two Educational Opportunities in Infants

The objective of the study is to see whether early feeding of potentially allergic foods can be increased with educational materials alone or with educational materials and additional in-person support opportunities. This study will help guide what types of support pediatricians and allergists give to new parents.

Trophallergen Prick Tests (PT) : Influence of Food Sample Shelf Life on the Reproducibility of PT Results

Prick tests (PT) are the standard skin tests used in the investigation of immediate IgE-mediated food allergies. Their use as a first-line tool in allergological investigations is strongly recommended by the European Academy of Allergy and Clinical Immunology (EAACI). These tests involve locally reproducing histamine release manifestations in the epidermis by superficially introducing an allergen to confirm or rule out its role in the onset of clinical symptoms compatible with an allergy. During the diagnostic management and follow-up of patients with food allergies, the technique used is the "prick to prick" method, due to the lack of reliable access to many standardized commercial food extracts. This method involves piercing the food with a sterile lancet (to deposit food content on its surface) and then making a superficial skin puncture with the same device on the anterior surface of the forearm to introduce a tiny fraction of the food and its proteins into the epidermis, where mast cells are present. Simultaneously, a positive control and a negative control are performed. The tests are read after 15 to 20 minutes by measuring the size in millimeters of the resulting papules and erythema. A PT for the tested allergen is considered positive if the average diameter of the resulting papule is 3 mm or more and/or at least half the size of the positive control papule. The procedure is well-tolerated, allowing it to be performed at any age, in both hospital and outpatient settings. The risk of a systemic reaction has been evaluated at 0.008%, with no severe reactions observed. This method, performed with native foods (unprocessed food, uncontaminated foods), either raw or cooked (depending on the nature of the allergen being tested), is preferred over the use of commercial extracts (standardized commercial allergen preparations) due to its better sensitivity and specificity, the high cost of commercial extracts, and the lack of commercial extracts for certain foods. For practical reasons, given the wide variety of possible allergens, and to most accurately reproduce the exposure that caused the reaction, the most common approach is to ask the patient to bring their own foods for testing. These foods should be brought in a fresh state. However, situations where the patient is offered a food PT but does not have fresh native foods are common. Indeed, many patients forget to bring them. Similarly, during a consultation to explore a respiratory or drug allergy, the interview may lead to the detection of a food allergy that needs to be tested at the same time. Given the delays in allergology consultations, the severity of food allergy symptoms, and the potential risk of delayed diagnosis, all allergists involved in managing food allergies are led to create a library of food samples stored either in a dry state (e.g., nuts, peanuts, cereal flours) or frozen for perishable foods (meats, shellfish, fruits, vegetables). To our knowledge, after reviewing the literature, no guidelines for best practices regarding the storage of these food samples for PT purposes have been established by scientific societies. Moreover, while the impact of freezing and thawing methods on the denaturation of food proteins is known, the effect of freezing and its duration on the sensitivity and specificity of PT is poorly understood. The objective of our study is to evaluate the reproducibility of PT results between those performed with fresh foods and those performed with preserved foods at different storage dates in participants who have experienced anaphylaxis of at least grade 2 according to the Ring and Messmer classification.

Can Vitamin D Supplementation in the First Year of Life Prevent Food Allergy in Infants? The VITALITY Trial: Parts 1&2

We report that Australia has the highest prevalence of Immunoglobulin(Ig)E-mediated food allergy in the world, with 10% of infants having challenge-proven food allergy in Melbourne. There has been a 5-fold increase in hospital admissions for life-threatening anaphylaxis. These changes are most pronounced in children less than 5 years, suggesting a causal role for early life determinants. We have primary data to inform hypotheses for the rise in food allergy, which appears to result from potentially modifiable factors related to the modern lifestyle, particularly Vitamin D insufficiency (VDI). We propose an intervention study to assess if infant Vitamin D supplementation during the first year of life significantly decreases the risk of early-onset food allergy and other allergic disease at 12 months (part 1) and 6 years of age (part 2). Australia is ideally placed to answer this important question since, unlike the USA, Canada and Europe, there are no population recommendations for routine infant supplementation with Vitamin D and we are one of the few developed countries that do not supplement the food chain supply with Vitamin D.

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.

Prescreening Protocol to Enroll in Food Allergy Clinical Studies at a Single Site

This is a protocol for prescreening of participants who would like to be in clinical studies in our Center at Stanford.

EmoTIChealth: Promoting Adolescent Health Through a Serious Game.

The intervention program targets adolescents between 12 and 16 years of age. The intervention program is designed for adolescents during a critical developmental stage marked by significant life transitions, where building strong personal resources and receiving psychological support is essential to foster socioemotional skills and overall well-being. The serious game aims to promote psycho-emotional health in the general adolescent population, supporting healthy development and preventing future emotional difficulties. At the same time, it incorporates specific modules for adolescents living with chronic conditions such as asthma, food allergy, type 1 diabetes, and allergic rhinitis, who may face additional risks of psychological challenges that can complicate treatment and prognosis. By combining universal health promotion with tailored support, the program addresses both the needs of healthy adolescents and those with chronic illnesses. The platform integrates digital and technological tools for dynamic and personalized intervention. Artificial intelligence adapts activities and feedback to each participant's socio-demographic profile and evolving needs, this supports directly in participants' daily lives and natural environments, making the experience more relevant and impactful. The serious game, proven effective in engaging young people, goes beyond traditional psychoeducation by creating an interactive environment where adolescents develop socio-emotional competencies, resilience, and health-related knowledge. Through its six thematic areas, the game promotes overall well-being and healthy habits, while its condition-specific modules provide targeted guidance and coping strategies for asthma, food allergies, type 1 diabetes, and allergic rhinitis.

Michigan Food and Atopic Dermatitis (M-FAD) Program - Molecular Analytics Project

This study will explore potential links between atopic dermatitis and food allergy. This information will be useful to determine atopic dermatitis and food allergy share unique biochemical or genetic identifiers useful for diagnosing and treatments in the future. This is a mechanistic study consisting of obtaining blood and skin samples from participants at baseline. Individuals may also undergo a clinically indicated oral food challenge and have blood and skin samples collected at various times during the oral food challenge. This study will create a molecular map of the pathology of atopic dermatitis and food allergy. This information will be deployed to evaluate the hypothesis that atopic dermatitis and food allergy share unique genetic transcriptional signals in which the study team can then further analyze pathological pathways and cell types.

The Egg Up Trial - Testing a New Treatment Pathway for Infants With Newly Diagnosed Egg Allergy

The goal of this study is to test the safety and feasibility of a change in management approach for infants with newly diagnosed egg allergy. Infants with newly diagnosed egg allergy will have egg introduced via a gradual and graded home based approach known as an "egg ladder" supervised by a dietitian. The main questions this study aims to answer are how safe and feasible are home-based dietitian-led "egg ladders" as a treatment pathway to achieve tolerance of egg for newly diagnosed infants with egg allergy.

Short-Term Linvoseltamab Treatment on Top of Chronic Dupilumab Treatment for Adults With Severe Immunoglobulin E (IgE)-Mediated Food Allergy

This study is researching an experimental drug called linvoseltamab combined with another drug called dupilumab. The study is looking at patients who have severe IgE-mediated food allergy. If the patient has an allergy, the body's defense system (immune system) overreacts to an allergen (eg, certain foods like peanuts, milk, shellfish) by making antibodies called IgE. An antibody is a protein that allows the immune system to find and fight off things the body does not recognize (allergens). IgE antibodies are sent out by cells like plasma cells. These antibodies and allergens bind to other cells that send out chemicals, causing an allergic reaction. The aim of the study is to see what side effects happen when linvoseltamab is combined with dupilumab. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * Does linvoseltamab combined with dupilumab affect other types of antibodies in the blood at different times * How much study drug(s) is in the blood at different times

Analysis of the Prevalence of Sensitization to Plants Containing Gibberellins Using Realistic Skin Prick Tests

Gibberellin-related proteins (GRPs) are proteins contained in both pollens and vegetables and are associated with an increased risk of severe food allergy reactions. The best characterized one the only one for which a specific IgE (Immunoglobulin E) may be dosed in current clinical practice is Pru p 7, an allergen contained in peaches (Prunus persica). Sensitization to GRPs seems to be greater in areas with high exposure to pollens of the Cupressaceae family (as in the Montpellier region in Southern France); a subtype of Cupressaceae pollinosis, characterized by sensitization to Pru p 7 has been shown to be responsible for severe peach allergies. To date, there has been no real analysis of the prevalence of sensitization to GRPs, or of possible cross-sensitization between plants and foods containing GRPs. Main food containing GRPs with a high level of homology with Pru p 7 include apples (Malus domestica, 97.3%), sesame (Sesamum indicum, 91.9%), carrots (Daucus carota subsp. Sativus, 88.9%), lemons and oranges (different species, with a homology of 87.3%). If investigators consider that sensitization to GRPs could be associated with severe allergic hypersensitivity reactions, it is important to detect the prevalence of sensitization to these allergens and to find sensitization profiles for these patients in order to gain a better understanding of this type of allergy and offer a more appropriate and preventive management to allergic patients. This remains today a major challenge for the allergy community in the Mediterranean region. This study aims to investigate the rate of sensitization to peach and 5 other allergens containing gibberellins, chosen on the basis of their homology with Pru p 7 (the gibberellin from Prunus persica): carrot, lemon, orange, apple and sesame.

Molecular Basis of Food Allergy

The Study examines the molecular basis of food allergy. It explores the interaction between T cells, InKT cells, basophils and cytokines in the development of food allergy. The study also explores these factors in development of tolerance "outgrowing" food allergy. It will also explore the genetic factors that lead to the development of food allergy. The study examines all type of food allergy including IgE mediated reactions, Eosinophilic Esophagitis and Food Protein Induced Enterocolitis

Data and Sample Collection Study to Elucidate the Mechanisms of Eosinophilic Disorders

The purpose of this study is to elucidate the mechanisms underlying eosinophil growth, survival, migration, and function and to investigate and further characterize the pathophysiology of, clinical manifestations of, and spectrum of disease severity of eosinophilic inflammation in humans.

Oral Immunotherapy in Young Children With Food Allergy

The goal of this clinical trial is to learn about oral immunotherapy in food allergic children \< 30 months of age. The main question it aims to answer is: What is the clinical- and cost-effectiveness of early low-dose oral immunotherapy aimed at long-term tolerance induction. Participants will receive oral immunotherapy for 1 year with a maintenance dose of 300 mg allergenic protein and are compared with food allergic infants not receiving oral immunotherapy to compare with natural tolerance development.

Randomized Controlled Trial of Slow Multiallergen Oral Immunotherapy in Young Children

The aim is to study whether a multiallergen oral immunotherapy (OIT) strategy with slow up-dosing and low treatment dose against food allergy in young children (0.5-3 years) is safe and effective, a method to cure food allergy and to prevent the development of new food allergies. Clinical randomized controlled (1:1) blinded interventional trial (RCT) with 2 intervention arms (group A and B). Among 80 children reacting at the multiallergen food challenge, 40 children will be randomized to receive OIT (oral immunotherapy) with multiallergen powder with a final dose of approximately 200 mg protein of each included food (egg, milk, soy, wheat, walnut, peanut, hazelnut, cashew, almond, lentils)(group A) or to receive placebo powder (gluten-free oatmeal) (group B). A sub-analysis will be performed of the children not reacting to the baseline challenge, who will be randomized to eat a low dose of the multiallergen powder (group C) or placebo powder (gluten-free oatmeal) (group D) and no specific advice.

Evaluating the Safety and Efficacy of Oral Encapsulated Microbiota Transplantation Therapy in Peanut Allergic Patients

This is a phase II trial that aims at evaluating the safety and tolerability of oral encapsulated fecal microbial transplantation therapy (MTT) in peanut allergic patients. In this research the investigators would like to learn more about ways to treat peanut allergies. The primary objective for Part A is to evaluate whether MTT with antibiotic pretreatment can increase the threshold of peanut reactivity during a double-blind placebo-controlled food challenge from \<=100 mg peanut protein to 300 mg after 28 days of MTT /placebo therapy and 4 months post therapy initiation. The primary objective for Part B is to evaluate whether MTT with antibiotic pretreatment can lead to sustained unresponsiveness (SU) defined as tolerating the same dose of peanut protein administered during a food challenge at baseline and 12 weeks after OIT cessation.

FeNO as a Marker of Allergic Reactions to OFC and Response of OMA Treatment in Multiple FA

This is a Phase IV, open-label, single-center study to evaluate the change in FeNO as a marker of clinical response to OMA in participants with multiple FA.

Early Supplementation for Cow's Milk Allergy Prevention

Cow's milk allergy (CMA) is a common food allergy in infants and young children that can have a significant impact on the individual and their family due to dietary restrictions, risk of nutritional deficiencies, social limitations, and decreased quality of life. It also represents a financial burden for families and healthcare resources. There is an ongoing debate about the significance of early exposure to cow's milk proteins within hours or days after birth and its relationship to the risk of developing CMA later in life. Current recommendations for early introduction of cow's milk proteins in infants who cannot be breastfed vary and are inconsistent due to a lack of clear evidence. This knowledge gap underscores the need for further research to provide a definitive understanding of the relationship between early exposure to cow's milk proteins and the development of CMA, which will ultimately inform evidence-based prevention strategies to improve the health and well-being of affected individuals and their families. This trial aims to investigate whether early supplementation with various nutritional interventions (cow's milk formula \[CMF\], amino acids formula \[AAF\], donor human milk \[DHM\], or high-pressure processed "pascalized" donor human milk \[DHM-P\]) could serve as an effective strategy for the primary prevention of CMA in breastfed neonates. This study is an open-label randomized, controlled, head-to-head trial with four parallel arms and allocation 1:1:1:1.

Efficacy and Safety of Egg Ladders in Children With IgE-Mediated Hen's Egg Protein Allergy

Hen's Egg Allergy is one of the most common food allergies in early childhood. The first-line treatment is the elimination of hen's egg proteins from the child's or maternal diet. Available data from the literature indicate that most children with hen's egg allergy acquire tolerance to hen's egg proteins with age. An assessment of tolerance acquisition to them is commonly performed using egg ladder. However, scientific evidence regarding the effectiveness and safety of the egg ladder in children with hen's egg allergy is limited. Currently, there is no standardised egg ladder protocol, and different versions of the ladder and recommend by scientific societies in various countries. This study aims to assess the effectiveness and safety of the 4-step egg ladder (4-EL) compared to the 5-step egg ladder (5-EL) in children with IgE-mediated hen's egg allergy. This is an open-label, randomised superiority trial with two parallel arms and a 1:1 allocation ratio.

Pectin Intervention Study and Long-term Follow-up in Lipid Transfer Proteins Allergic Patients

Pectins are dietary fibers that have shown a health effect on patients with food allergy, as they are capable of modifying the composition of gastrointestinal microbiota, and producing an immunomodulatory effect. Preliminary results by the investigators show that the intervention for 2 months with pectins produces an increase in tolerance to peach, and changes in the microbiota compared to the group of patients treated with placebo. In this project, the investigators aim to study these clinical effects and the involved mechanisms. Moreover, the long-term effect (clinical reactivity to nsLTP and immunomodulatory effect) of the dietary intervention will be prospectively evaluated 6 months after the intervention.