Immune Basis and Clinical Implications of Threshold-based Phenotypes of Peanut Allergy

NCT ID: NCT03907397

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-05
• Study Completion Date: 2023-11-17

Brief Summary

The primary objective of this study is to determine whether allowing ingestion of sub-threshold amounts of peanut in those with a high threshold (tolerate at least 143 mg peanut protein on supervised double-blind, placebo-controlled oral food challenge [DBPCFC]) will be associated with attaining even higher thresholds over time in children with high threshold peanut allergy compared to those avoiding peanut. The secondary clinical objectives include assessing the development of sustained unresponsiveness (SU, a surrogate term for tolerance without daily ingestion), effects on quality of life, and safety compared to those avoiding peanut. Additionally, this study will phenotype the allergic response to peanut based on threshold and response to exposure. Mechanistic study objectives will determine the immune and molecular basis of the high threshold endotype, identify predictors of response to exposure, and determine mechanisms and biomarkers of remission.

Conditions

Food Allergy; Peanut Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Ingests peanut - . Depending upon reaction threshold, participants may begin with different starting amounts of store bought peanut butter measured with study-supplied kitchen measuring spoons.

Group Type: ACTIVE_COMPARATOR

Peanut Protein

Intervention Type: BIOLOGICAL

up to 3 level teaspoons peanut butter or equivalent (approximately 3400 mg)

Avoidance

Avoids peanut, standard care

Group Type: OTHER

Continued peanut avoidance

Intervention Type: OTHER

Standard of care avoidance of peanut

Interventions

Peanut Protein

up to 3 level teaspoons peanut butter or equivalent (approximately 3400 mg)

Intervention Type: BIOLOGICAL

Continued peanut avoidance

Standard of care avoidance of peanut

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

-Subject and/or parent guardian must be able to understand and provide informed consent.

• Age 4-14 years
• either sex
• any race, any ethnicity
• who are enrolled while strictly avoiding peanut
• have a history of sensitization (detectable peanut IgE >0.35 kUA/L)

• On screening DBPCFC are able to ingest >= 143 mg peanut protein but < 5043 mg peanut protein.
• All children will have documented consent and assent as is appropriate for age.

Exclusion Criteria

Individuals who meet any of these criteria are not eligible for enrollment as study participants:

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Serum peanut-specific IgE antibody level > 50 kUA/L
• Recent (within the past 2 years) life-threatening (grade 3) anaphylactic reaction to peanut.
• Any disorder in which epinephrine is contraindicated such as known hypertension or cardia rhythm disorders.
• History of chronic disease requiring therapy (other than asthma, atopic dermatitis, rhinitis).
• On a build-up phase of any allergen immunotherapy.
• For those with a history of asthma, the following are assessed and any of the following is an exclusion (markers of current uncontrolled or moderate to severe asthma):

1. FEV1 value <80% predicted (only for participants age 7 years or older and are able to perform spirometry)

2. ACT or cACT < 20

3. >Step 3 controller therapy as defined for children 0-4, 5-11 and >=12 years of age by EPR-3 tables

4. Use of steroid medications in the following manners:

1. history of daily oral steroid dosing for >1 month during the past year,

2. having 1 burst or steroid course within the past 6 months, or

3. having >1 burst oral steroid course within the past 12 months.

5. Asthma requiring >1 hospitalization in the past year for asthma or >1 ED visit in the past 6 months for asthma, or any prior intubation/mechanical ventilation for asthma/wheezing.

6. When COVID related institutional restrictions on spirometry are in effect, spirometry will not be performed and peak flow will be used with 80% predicted as cut-off.

• Gastrointestinal eosinophilic disorders, esophagitis, gastroenteritis.
• Use of short-acting antihistamines (diphenhydramine, etc.) more than one time within 3 days prior to DBPCFC or skin testing.*
• Use of medium-acting antihistamines (hydroxyzine, loratadine, etc.) more than one time within 7 days of DBPCFC or skin testing.*
• Use of systemic steroid medications (IV, IM or oral) for indications other than asthma for > 3 weeks within the past 6 months
• Use of beta-blockers (oral), (ACE) inhibitors, angiotensin-receptor blockers or calcium channel blockers.
• Participation in any trials of therapeutic interventions for food allergy in the past year.
• Therapy with anti-IgE or other biologics, including within 1 year of enrollment.
• Use of investigational drugs within 52 weeks of participation.
• Allergy to all of the following: oat, rice, corn, tapioca.
• Pregnancy
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

*Any subject meeting these criteria during the visits can be rescheduled for the oral food challenge or prick skin testing.*

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Scott Sicherer

OTHER

Sponsor Role: lead

Responsible Party

Scott Sicherer

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Scott Sicherer, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Countries

United States

References

Sicherer SH, Bunyavanich S, Berin MC, Lo T, Groetch M, Schaible A, Perry SA, Wheatley LM, Fulkerson PC, Chang HL, Suarez-Farinas M, Sampson HA, Wang J. Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy. NEJM Evid. 2025 Mar;4(3):EVIDoa2400306. doi: 10.1056/EVIDoa2400306. Epub 2025 Feb 10.

Reference Type: DERIVED

PMID: 39928078 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

U19AI136053

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 17-0722

Identifier Type: -

Identifier Source: org_study_id