IgE Threshold Testing for Food Allergy

Recruiting in Palo Alto (17 mi)

Overseen by Pamela A Guerrerio, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Beta-blockers, Omalizumab, Dupilumab

Disqualifiers: Pregnancy, Cardiac disease, Eosinophilic GI, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Background: Atopic dermatitis (AD), also called eczema, makes skin dry, red, and itchy. People with AD are more likely to get a food allergy than people without AD. But some food allergy tests are not always accurate in people with AD. Researchers want to study if people are truly allergic to milk and/or peanuts. Objectives: To improve the ways doctors test for food allergy in people with AD. Eligibility: People ages 3 21 who have had AD; have a high total IgE level (an allergic antibody); might have a milk and/or peanut allergy; and are currently enrolled in another NIH study Design: Participants will be screened under another protocol. Participants will have a physical exam, blood tests, and medical history. Participants will breathe into a plastic device that measures lung strength. Participants may get a small plastic tube inserted in their arm. Participants who have not had an allergic reaction to food in the past 3 years will do 1 or more oral food challenge (OFCs) depending on their allergies. They will eat a little bit of the food they might be allergic to. They will be watched for a reaction. If they have one, they will know for sure they are allergic. They may keep eating bigger portions of the food until they either have a reaction or finish all the food. In some OFCs, participants will get a placebo food. OFCs will last a few hours or 2 days. Participants will repeat all tests at each OFC. Participation can last up to 12 months. ...

Will I have to stop taking my current medications?

You may need to stop taking certain medications like omalizumab or dupilumab at least 6 months before a food challenge, and you might need to stop antihistamines and oral steroids before the challenge as well. However, you can continue using topical steroids.

What data supports the effectiveness of the treatment Baked milk and Rice milk (placebo for Baked milk), Baked milk, Heated milk, Rice milk (as placebo), Dry Milk Powder and Corn Starch (placebo for Milk powder), Dry Milk Powder, Milk Powder, Corn Starch (placebo), Peanut flour and Oat flour (placebo for peanut flour), peanut flour, oat flour (placebo), Peanut powder and Oat flour, Peanut powder: Arachis hypogaea, Groundnut powder; Oat flour: Avena sativa flour for food allergy?

Research shows that many children with cow's milk allergy can tolerate baked milk, which may help them eventually tolerate regular milk. Introducing baked milk gradually can speed up the resolution of milk allergies in some children. ^{1 2 3 4 5}

Is there safety data for IgE Threshold Testing for Food Allergy treatments like Baked milk, Rice milk, and Peanut flour?

Research shows that peanut allergen powder used in oral immunotherapy has been evaluated for safety in clinical trials, indicating it is generally safe for use in humans. However, hypoallergenic milk substitutes may contain aflatoxin, a potential contaminant, so control measures should be in place to ensure safety. ^{6 7 8 9 10}

How does IgE Threshold Testing for Food Allergy differ from other treatments for food allergies?

IgE Threshold Testing for Food Allergy is unique because it focuses on determining the specific level of IgE antibodies (immune system proteins that react to allergens) that trigger allergic reactions, which can help tailor dietary recommendations and predict safe food consumption, unlike standard treatments that often involve complete avoidance of allergens. ^{1 8 11 12 13}

Research Team

Pamela A Guerrerio, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

This trial is for children and young adults aged 3-21 with atopic dermatitis (eczema) who may have milk or peanut allergies, a high total IgE level, and are part of another NIH study. They must be willing to stop certain allergy medications before food challenges.

Inclusion Criteria

You have been diagnosed with Alzheimer's disease by a doctor or you have reported having symptoms of Alzheimer's disease.

I am willing to have genetic tests done on my blood.

Willing to allow storage of blood samples for future use in medical research.

Exclusion Criteria

I have a known heart condition.

I am on long-term oral steroids for a chronic condition.

I am currently taking a beta-blocker medication.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Oral Food Challenge

Participants undergo open feedings and/or double-blind, placebo-controlled food challenges to assess food allergies

Up to 12 months

Multiple visits for each food challenge

Follow-up

Participants are monitored for safety and effectiveness after food challenges

4 weeks

Treatment Details

Interventions

• Baked milk and Rice milk (placebo for Baked milk) (Other)
• Dry Milk Powder and Corn Starch (placebo for Milk powder) (Other)
• Peanut flour and Oat flour (placebo for peanut flour) (Other)
• Peanut powder and Oat flour (Other)

Trial Overview The trial tests if participants with eczema are truly allergic to milk or peanuts by giving them increasing amounts of these foods or placebos in controlled settings. The goal is to improve food allergy testing methods.

Participant Groups

Group I: Two-Step Open Feeding Experimental Treatment 4 Interventions

Participants who consume baked milk, straight milk, and/or peanut products less than once per week but at least once per month will do a two step open oral food challenge.

Group II: Peanut DBPCFC Experimental Treatment 2 Interventions

The DBPCFC for peanut allergy will be done with either peanut flour or a placebo (oat flour). The following participants will undergo this DBPCFC: - All participants who eat peanut less than once per month - Participants who never eat peanut On the first day of this challenge, participants will be randomized to either peanut or placebo, and then will be challenged with the other food on the next day.

Group III: One-Step Open Feeding Experimental Treatment 4 Interventions

Participants who are consuming baked milk, straight milk, and/or peanut products at least once per week will do a one-step oral food challenge.

Group IV: Milk DBPCFC Experimental Treatment 2 Interventions

There are two double blind placebo controlled food challenges. The first challenge is to baked milk. The following participants will undergo this DBPCFC: - All participants who eat baked milk less than once per month. - Participants who never eat baked milk or straight milk. On the first day of this challenge, participants will be randomized to either milk Baked milk or rice milk. Dry milk powder or corn starch. or placebo, and then will be challenged with the other food on the next day.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

National Institutes of Health Clinical Center (CC)

Collaborator

Trials

391

Recruited

30,880,000+

Pius Aiyelawo

National Institutes of Health Clinical Center (CC)

Chief Executive Officer

MPA, FACHE

Dr. Karen Frank

National Institutes of Health Clinical Center (CC)

Chief Medical Officer

MD

Findings from Research

Skin prick testing (SPT) with a baked milk (muffin) slurry can effectively predict which milk-allergic children can safely consume baked milk, showing a sensitivity of 100% for those with negative tests.

In a study of 30 children aged 2-16 years, those with a muffin SPT result of less than 3 mm were likely to tolerate baked milk, while the optimal decision point for the test was determined to be 4 mm, indicating its potential utility in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children. Kwan, A., Asper, M., Lavi, S., et al.[2020]

In a study of 64 children with severe cow's milk allergy, 67.2% tolerated a low-dose baked milk oral food challenge, indicating that baked milk oral immunotherapy (OIT) can be effective for many children.

Desensitization to fresh milk was achieved in 42.2% of the children, particularly those with lower cow's milk-specific IgE levels, although there remains a risk of anaphylactic reactions during the OIT process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of baked milk oral immunotherapy in French children with cow's milk allergy. Gruzelle, V., Juchet, A., Martin-Blondel, A., et al.[2021]

In a study of 48 children with IgE-mediated cow's milk allergy, 81% tolerated baked cow's milk when it was incorporated into a wheat matrix (ciambellone), indicating that the wheat matrix significantly aids in tolerance.

The study found that a negative prick-by-prick test (PbP) had a 100% negative predictive value, suggesting that if the test is negative, children can safely consume processed cow's milk without needing an oral food challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matrix effect on baked milk tolerance in children with IgE cow milk allergy. Miceli Sopo, S., Greco, M., Monaco, S., et al.[2017]

Approximately 70% of children who are allergic to unheated milk or egg can tolerate extensively heated versions of these foods, suggesting that including baked forms in their diet may help them develop tolerance more quickly than strict avoidance.

Oral food challenges (OFC) and oral immunotherapies (OIT) using low doses of allergenic foods could be a promising strategy to improve tolerance and quality of life for patients with food allergies, especially since current OIT methods often lead to unsatisfactory results and require long-term commitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies. Yanagida, N., Okada, Y., Sato, S., et al.[2022]

In a study involving 25 cow's milk allergic children aged 3 to 36 months, 72% tolerated a new standardized heated cow's milk protein (HP) product, suggesting it may help in developing tolerance to cow's milk.

Risk factors for intolerance included higher skin prick test results and specific IgE levels against certain milk proteins, indicating that these tests could help predict which children might have adverse reactions to the HP product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children: The iAGE Study. de Jong, NW., van Splunter, ME., Emons, JAM., et al.[2022]

In a 6-month phase 3 trial involving 506 children with peanut allergies, PTAH (peanut allergen powder-dnfp) demonstrated a safety profile similar to that observed in previous trials that required double-blind, placebo-controlled food challenges (DBPCFCs).

The most common treatment-emergent adverse events (AEs) were mild to moderate gastrointestinal issues, with 55% of PTAH participants experiencing at least one AE compared to 33.9% for placebo, indicating that while AEs were common, they were generally not severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Participant characteristics and safety outcomes of peanut oral immunotherapy in the RAMSES and ARC011 trials. Ciaccio, C., Goldsobel, AB., Anagnostou, A., et al.[2022]

Aflatoxin B1 was found in hypoallergenic milk substitutes made from ingredients like soya protein isolate and corn syrup, but most levels were below 1 ng/ml, which is considered low risk.

Manufacturers' reserve samples of soya protein isolate were uncontaminated, suggesting that while contamination is possible, it may not be widespread; however, caution is advised due to the vulnerability of infants relying on these formulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of Aflatoxin in Hypoallergenic Milk Substitutes. Hayes, AW., Unger, PD., Stoloff, L., et al.[2023]

Three patients developed asthma due to exposure to cereal flours in animal formula feeds, confirmed by positive skin prick tests and specific IgE antibodies to wheat, rye, and barley.

Bronchial provocation tests demonstrated immediate asthma responses to wheat and barley flours, indicating that these cereal flours can cause IgE-mediated hypersensitivity and highlighting their role as a potential occupational asthma trigger for farm workers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Farm animal feeders: another group affected by cereal flour asthma. Valdivieso, R., Pola, J., Zapata, C., et al.[2019]

A patient with baker's asthma was found to have a rice allergy, indicating a potential cross-reactivity between wheat proteins and similar proteins in rice.

Specific IgE reactivity to wheat alpha-amylase/trypsin inhibitor and lipid transfer protein suggests that the rice allergy may be triggered by homologous molecules present in rice seeds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of rice allergy in a patient with baker's asthma. Villalta, D., Longo, G., Mistrello, G., et al.[2015]

The manufacturing process of peanut allergen powder (PTAH) for oral immunotherapy is critical for ensuring drug safety and efficacy, as variability in peanut flour sourcing and processing can affect allergen potency and contamination levels.

Despite challenges such as seasonal variability and aflatoxin contamination, stringent manufacturing controls are in place to maintain consistent allergenic potency and quality, ensuring that PTAH is safe and effective for treating peanut allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manufacturing processes of peanut (Arachis hypogaea) allergen powder-dnfp. Leonard, SA., Ogawa, Y., Jedrzejewski, PT., et al.[2022]

In a study of 16 patients, only 6 showed true corn allergy symptoms confirmed by a double-blind, placebo-controlled food challenge (DBPCFC), highlighting the need for this rigorous testing to confirm corn allergies.

A 50 kDa protein from the corn Reduced Soluble Protein (RSP) fraction was identified as a potential allergen, as it was recognized by IgE in all DBPCFC-positive patients and remained stable during cooking and digestion, suggesting it could trigger allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgE-mediated allergy to corn: a 50 kDa protein, belonging to the Reduced Soluble Proteins, is a major allergen. Pasini, G., Simonato, B., Curioni, A., et al.[2019]

In a study involving 20 pediatric patients with asthma and/or eczema, specific IgE binding was found to be strongest with wheat, rye, and barley proteins, particularly the globulins and glutenins from wheat, indicating their significant role in allergic reactions.

Partial digestion of flour proteins significantly reduced their ability to bind IgE, suggesting that the structure of these proteins is crucial for their allergenic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin E antibodies to ingested cereal flour components: studies with sera from subjects with asthma and eczema. Sutton, R., Hill, DJ., Baldo, BA., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Prospective evaluation of testing with baked milk to predict safe ingestion of baked milk in unheated milk-allergic children. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Benefits of baked milk oral immunotherapy in French children with cow's milk allergy. [2021]

3. Singapore pubmed.ncbi.nlm.nih.gov

Matrix effect on baked milk tolerance in children with IgE cow milk allergy. [2017]

4. England pubmed.ncbi.nlm.nih.gov

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Introduction of Heated Cow's Milk Protein in Challenge-Proven Cow's Milk Allergic Children: The iAGE Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Participant characteristics and safety outcomes of peanut oral immunotherapy in the RAMSES and ARC011 trials. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Occurrence of Aflatoxin in Hypoallergenic Milk Substitutes. [2023]

8. Denmark pubmed.ncbi.nlm.nih.gov

Farm animal feeders: another group affected by cereal flour asthma. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

A case of rice allergy in a patient with baker's asthma. [2015]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Manufacturing processes of peanut (Arachis hypogaea) allergen powder-dnfp. [2022]

11. Denmark pubmed.ncbi.nlm.nih.gov

IgE-mediated allergy to corn: a 50 kDa protein, belonging to the Reduced Soluble Proteins, is a major allergen. [2019]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Diagnosis and management of grain-induced asthma. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Immunoglobulin E antibodies to ingested cereal flour components: studies with sera from subjects with asthma and eczema. [2019]