Persistence of Oral Tolerance to Peanut

Study Overview
=================
Brief Summary
-----------------
ITN049AD (LEAP-On) Study is a continuation of the ITN032AD LEAP Study (NCT00329784). Peanut Allergy, a recognized public health concern, is a common and potentially life-threatening food allergy for which there is no treatment. ITN032AD (LEAP) Study evaluated whether early exposure to peanut promotes tolerance and provides protection from developing peanut allergy in children who are allergic to eggs or who have severe eczema. ITN049AD (LEAP-On) Study will evaluate persistent tolerance to peanut by assessing the effect of twelve months of cessation of peanut consumption in LEAP Study participants who consumed peanut and those who avoided peanut over the previous five years.

Detailed Description
-----------------
This is a two-sample comparison employing all available study participants in both arms of the LEAP (NCT00329784) study at visit 72. After obtaining informed consent, LEAP participants who are evaluable for peanut allergy at age 60 months (V60) will be enrolled into this study, the LEAP-On (NCT01366846) Study. All LEAP-On participants will avoid peanut for an additional 12 months regardless of their previous allocation to the LEAP Study consumption arm (Group A) or the LEAP Study avoidance arm (Group B). At V72, after 12 months of this new intervention, all participants will have skin prick testing (SPT), specific IgE and a repeat oral challenge to peanut to determine the frequency of peanut allergy in both groups. The LEAP Study decision table will be used to determine the presence of peanut allergy. Briefly, peanut allergy will be based on the presence of a positive oral peanut challenge with objective signs of allergy. Tolerance will be established on the basis of a negative oral peanut challenge (tolerating 5 g of peanut protein in the absence of symptoms). For participants who do not have an oral challenge or an oral challenge at V72 with a determinate outcome, the following criteria will be used to determine their outcome at V72: If the participant is tolerant and has an IgE > 0.1 and/or SPT > 0 mm at V60, the participant will be considered non-evaluable and will not be included in the analysis. For all other participants, the V60 outcome will be applied to the V72 outcome (last observation carried forward). Predictive values of peanut-specific IgE and/or SPT will not be used in the LEAP-On study because participants in the peanut consumption arm in the LEAP study are tolerating peanuts despite having high IgE and/or SPT.

Official Title
-----------------
The Persistence of Oral Tolerance Induction to Peanut and Its Immunological Basis (ITN049AD)

Conditions
-----------------
Eczema, Egg Allergy, Food Allergy, Hypersensitivity

Intervention / Treatment
-----------------
* Other: Avoidance of peanut


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All LEAP Study participants who are evaluable for peanut allergy at year 5 by LEAP (ClinicalTrials.gov ID NCT00329784) Study criteria. Parent or guardian willing to provide informed consent. Exclusion Criteria: Unable or unwilling to comply with study intervention and procedures. Participation in other food allergy intervention trials.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peanut avoidance after continuous peanut consumption<br>These participants were the peanut consumption group of the ITN032AD (LEAP) study | Other: Avoidance of peanut<br>* All participants will be assigned to peanut avoidance as per United Kingdom (UK) public health recommendations and will avoid exposure to peanut protein during the study until the last study visit when they will receive the Oral Food Challenge.<br>|
| Experimental: Continued peanut avoidance<br>These participants were the peanut avoidance group of the ITN032AD (LEAP) study | Other: Avoidance of peanut<br>* All participants will be assigned to peanut avoidance as per United Kingdom (UK) public health recommendations and will avoid exposure to peanut protein during the study until the last study visit when they will receive the Oral Food Challenge.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to not have peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. | 72 months | 
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. | 72 months | 
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have peanut allergy. | 72 months | 
| Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population | At 72 months of age, eligible participants were given an oral food challenge (oral intake of 5g of peanut protein in a single dose Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 13.7g of peanut protein administered in increments. These participants were to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. | 72 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group | At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. | 60 months and 72 months | 
| Number of Peanut Avoidance After Peanut Consumption Group Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within in the Per Protocol Population | At 60 and 72 months of age, eligible participants were given an oral food challenge (intake of 5g of peanut protein in a single dose). Participants were considered to have no peanut allergy (PA) if they experienced no reaction following the food challenge. Those who did react were offered a double-blind, placebo-controlled food challenge with a total of 9.4g/13.7g (month 60/month 72) of peanut protein administered in increments. These participants were considered to have PA if they experienced a reaction at any point during the dose escalation. For participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on the results of a SPT and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have PA. | 60 months and 72 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peanut