Persistence of Oral Tolerance to Peanut (LEAP-On)

• ClinicalTrials.gov Identifier: NCT01366846
• Recruitment Status: Completed
• First Posted: June 6, 2011
• Results First Posted: January 6, 2017
• Last Update Posted: March 10, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Eczema; Egg Allergy; Food Allergy; Hypersensitivity	Other: Avoidance of peanut	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 556 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Persistence of Oral Tolerance Induction to Peanut and Its Immunological Basis (ITN049AD)
• Study Start Date: May 2011
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Peanut avoidance after continuous peanut consumption; These participants were the peanut consumption group of the ITN032AD (LEAP) study	Other: Avoidance of peanut; 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.
Experimental: Continued peanut avoidance; These participants were the peanut avoidance group of the ITN032AD (LEAP) study	Other: Avoidance of peanut; 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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum [ Time Frame: 72 months ]
   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.
2. Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group [ Time Frame: 72 months ]
   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.
3. Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Skin Prick Test Stratum in the Per Protocol Population [ Time Frame: 72 months ]
   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.
4. Number of Participants With Peanut Allergy (PA) at 72 Months of Age - by Treatment Group in the Per Protocol Population [ Time Frame: 72 months ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Peanut Allergy (PA) at 60- and 72-month Visits Within the Peanut Avoidance After Peanut Consumption Group [ Time Frame: 60 months and 72 months ]
   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.
2. 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 [ Time Frame: 60 months and 72 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United Kingdom

Evelina Children's Hospital

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

• Study Chair: Gideon Lack, MD; Evelina Children's Hospital

More Information

Additional Information:

LEAP Study informational website  Immune Tolerance Network website  National Institute of Allergy and Infectious Diseases (NIAID) website 

Study Data/Documents: Individual Participant Data Set 

Identifier: LEAP-On (ITN049AD)

Study protocol synopsis; datasets and figures from published NEJM 2016 article 

Identifier: LEAP-On (ITN049AD)

Publications of Results:

Du Toit G, Sayre PH, Roberts G, Sever ML, Lawson K, Bahnson HT, Brough HA, Santos AF, Harris KM, Radulovic S, Basting M, Turcanu V, Plaut M, Lack G; Immune Tolerance Network LEAP-On Study Team. Effect of Avoidance on Peanut Allergy after Early Peanut Consumption. N Engl J Med. 2016 Apr 14;374(15):1435-43. doi: 10.1056/NEJMoa1514209. Epub 2016 Mar 4.

Other Publications:

Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, Brough HA, Phippard D, Basting M, Feeney M, Turcanu V, Sever ML, Gomez Lorenzo M, Plaut M, Lack G; LEAP Study Team. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015 Feb 26;372(9):803-13. doi: 10.1056/NEJMoa1414850. Epub 2015 Feb 23. Erratum in: N Engl J Med. 2016 Jul 28;375(4):398.

Santos AF, Du Toit G, Lack G. Is the use of epinephrine a good marker of severity of allergic reactions during oral food challenges? J Allergy Clin Immunol Pract. 2015 May-Jun;3(3):429-30. doi: 10.1016/j.jaip.2014.12.009.

Gruchalla RS, Sampson HA. Preventing peanut allergy through early consumption--ready for prime time? N Engl J Med. 2015 Feb 26;372(9):875-7. doi: 10.1056/NEJMe1500186. Epub 2015 Feb 23.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01366846 History of Changes
• Other Study ID Numbers: DAIT ITN049AD
• First Posted: June 6, 2011
• Results First Posted: January 6, 2017
• Last Update Posted: March 10, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: ITN049AD (LEAP-On) is a continuation of the ITN032AD LEAP Study. The plan is to share data in: 1.) ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.)TrialShare, a clinical trials research portal developed by the Immune Tolerance Network.

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Peanut

Additional relevant MeSH terms:

Hypersensitivity; Food Hypersensitivity; Egg Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate