Clinical trial NCT03907397: Immune Basis and Clinical Implications of Threshold-based Phenotypes of Peanut Allergy
Official title: Challenging to Food With Escalating Thresholds for Reducing Food Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Allergy
Peanut Allergy
Keywords: allergy
food
peanut
threshold
immunotherapy
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2019-04-09
Enrollment: 73
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 150-200 children undergoing DBPCFC to peanut to identify 72 with high threshold peanut allergy for randomization in trial.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Inclusion criteria for screening DBPCFC:

* 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)

Inclusion criteria for randomization:

* 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.\*

Primary outcomes:
measure: Percentage of Children That Tolerate the Full Challenge
timeFrame: 72 weeks
Secondary outcomes:
measure: The Percentage of Children That Achieve Sustained Unresponsiveness
timeFrame: 96 weeks
measure: Number of Children With Acute Allergic Reactions
timeFrame: 96 weeks
measure: Mean Change in Food Allergy Quality of Life Parental Burden Instrument
timeFrame: baseline and at 72 weeks
measure: Mean Change in SPT Wheal Size
timeFrame: Baseline and 72 weeks
measure: Mean Change in Peanut-specific IgE
timeFrame: Baseline and 72 weeks
measure: Mean Change in Peanut-specific IgG4
timeFrame: Baseline and 72 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Scott Sicherer, MD
role: PRINCIPAL_INVESTIGATOR
References: