Promoting Tolerance to Peanut in High-Risk Children (LEAP)

Induction of Tolerance Through Early Introduction of Peanut in High-Risk Children (ITN032AD)

This study will evaluate whether early exposure to peanuts promotes tolerance and provides protection from developing peanut allergy in children who are allergic to eggs or who have severe eczema.

This study has been continued into the ITN049AD (LEAP-On) Study (NCT01366846).

Study Overview

• Status: Completed
• Conditions: Egg Allergy; Eczema; Food Allergy
• Intervention / Treatment: Biological: Peanut Consumption Group

Detailed Description

Allergic reactions to peanuts are potentially life-threatening and, in some children, can result from ingestion of only trace quantities of peanuts. At highest risk are children with eczema or who are allergic to eggs; these children have a 20% chance of developing peanut allergy by the age of five. The majority of children allergic to peanuts have their first reaction between the ages of 14 and 24 months, often at the time of their first exposure to peanut. Currently, there is no cure for peanut allergy.

Peanut allergy has become an increasingly common problem in early childhood in the United States and the United Kingdom. Despite current public health guidelines in both countries recommending the avoidance of peanut consumption in the first years of life, the proportion of children with peanut allergy doubled in these countries over the period from 1998 to 2003. In contrast, peanuts are commonly consumed by infants in relatively high amounts in Africa, Southeast Asia and Israel, yet the rate of peanut allergy is quite low and does not appear to be increasing. Peanut consumption by infants in these parts of the world may actually protect children from developing peanut allergy by promoting oral tolerance to peanuts.

Participants in this study will be randomly assigned to either follow a peanut consumption regimen or a strict peanut avoidance regimen. Those assigned to the peanut consumption group will be asked to consume an age-appropriate snack three times a week for the duration of the study and will be monitored closely during their first introduction to peanut.

Those assigned to the peanut avoidance group will be asked to avoid ingestion of peanut for the first three years of life. A physical exam, allergy testing, and other immune system tests requiring blood collection will occur at Years 1, 3, and 5 following study entry. During the study, parents will maintain regular contact with study dietitians.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, SE1 7EH
      • Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 10 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to consume solid food
• Allergy to eggs and/or severe eczema
• Informed consent obtained from parent or guardian.

Exclusion Criteria:

• Clinically significant chronic illness. Participants with eczema or recurrent wheeze are not excluded.
• Positive skin prick test for peanut allergen with a wheel diameter greater than 4 mm in the presence of a negative saline control
• Previous or current consumption of peanut protein that exceeds 0.2 g of peanut protein on at least one occasion or 0.5 g over a single week
• Investigator-suspected allergy to peanut protein
• Investigator-suspected allergy to peanut protein in care provider or current household member.
• Diagnosis of persistent asthma
• ALT (SGPT) or bilirubin greater than 2 times the upper limit of age-related normal value
• BUN or creatinine greater than 1.25 times the upper limit of age-related normal value
• Platelet count less than 100,000/mL, hemoglobin less than 9 g/dL, or investigator-suspected immunocompromise
• Unwillingness or inability to comply with study requirements and procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Peanut Consumption Group; Participants on this arm will consume peanut protein.	Biological: Peanut Consumption Group; Peanut-containing snack. Children are to consume 2 g of peanut protein in three servings per week (total of 6 g) over 3 servings.; Other Names: Bamba
NO_INTERVENTION: Peanut Avoidance Group; Participants on this arm will avoid peanut as per United Kingdom (UK) public health recommendations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Peanut Allergy at 60 Months of Age - by Skin Prick Test Stratum	At 60 months of age, participants were given an oral food challenge Participants regarded as unlikely to be allergic to peanut received 5 g of peanut protein in a single dose. These participants were considered to have a peanut allergy if they experienced any type of reaction following consumption. A double-blind, placebo-controlled food challenge was offered to other participants with a total of 9.4 g of peanut protein administered in increments. These participants were considered to have a peanut allergy if at any point during the dose escalation procedure the participant had a reaction. Participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on clinical history, the results of a skin-prick test, and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have peanut allergy.	60 months
Number of Participants With Peanut Allergy at 60 Months of Age - Both Strata Combined	At 60 months of age, participants were given an oral food challenge Participants regarded as unlikely to be allergic to peanut received 5 g of peanut protein in a single dose. These participants were considered to have a peanut allergy if they experienced any type of reaction following consumption. A double-blind, placebo-controlled food challenge was offered to other participants with a total of 9.4 g of peanut protein administered in increments. These participants were considered to have a peanut allergy if at any point during the dose escalation procedure the participant had a reaction. Participants for whom data from the oral food challenge were either inconclusive or not available, a diagnostic algorithm based on clinical history, the results of a skin-prick test, and the values for peanut-specific IgE were used to determine whether or not a participant should be considered to have peanut allergy.	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SCORAD at 60 Months	At 60 months of age, participants were assessed for eczema using a modified Scoring Atopic Dermatitis System (SCORAD). This measure was used to detect eczema in children who may not have had access to topical anti-inflammatory medications or whose parents cannot recall or report the severity of their child's eczema. Eczema is any type of dermatitis or inflammation of the skin. Atopic dermatitis is the most severe and chronic of all types of eczema. The range of the SCORAD is 0-103. A score of 0 indicates no eczema, scores between 0 and 15 indicate mild eczema, scores between 15 and 40 indicate moderate eczema, and scores greater than 40 indicate severe eczema.	60 months
Number of Participants With Asthma at 60 Months	At 60 months of age, participants were assessed for asthma. Participants were considered to have asthma if they had a history of cough, wheeze, or shortness of breath that (1) was responsive to therapy with bronchodilators on two or more occasions in the previous 24 months, (2) required one visit to a physician in the previous 24 months, or (3) occurred during the night, during early morning, or upon exercising in the intervals between exacerbations at any time in the previous 12 months.	60 months
Number of Participants With Rhinitis at 60 Months	At 60 months of age, participants were assessed for rhinitis. Two types of rhinitis were assessed, perennial rhinoconjunctivitis and seasonal rhinoconjunctivitis. Participants were considered to have either type of rhinitis if they showed a sensitization to the allergen and clinical history of rhinoconjunctivitis symptoms experienced either when exposed to the relevant allergen (perennial) or during the relevant season (seasonal).	60 months
Number of Participants With Specific Skin Prick Test Greater Than or Equal to 3mm	At 60 months of age, participants were assessed for potential allergy to selected food allergens. Participants were considered to have a specific sensitivity if a skin prick containing the allergen produced a wheal size measuring greater than or equal to 3 mm.	60 months
Number of Participants With Food Specific IgE Greater Than or Equal to 0.35 kU/L	At 60 months of age, participants were assessed for potential allergy to selected food allergens. Participants were considered to have a specific food sensitivity if a blood draw showed specific IgE levels greater than or equal to 0.35 kU/L for selected ingested allergens.	60 months

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN)
• Investigators: Principal Investigator: Gideon Lack, MD, Imperial College, St. Mary's Hospital

Publications and helpful links

General Publications

• Palmer K, Burks W. Current developments in peanut allergy. Curr Opin Allergy Clin Immunol. 2006 Jun;6(3):202-6. doi: 10.1097/01.all.0000225161.60274.31.
• 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. No abstract available.
• 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.
• 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.
• 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. No abstract available.
• Du Toit G, Roberts G, Sayre PH, Plaut M, Bahnson HT, Mitchell H, Radulovic S, Chan S, Fox A, Turcanu V, Lack G; Learning Early About Peanut Allergy (LEAP) Study Team. Identifying infants at high risk of peanut allergy: the Learning Early About Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol. 2013 Jan;131(1):135-43.e1-12. doi: 10.1016/j.jaci.2012.09.015. Epub 2012 Nov 19.
• Feeney M, Du Toit G, Roberts G, Sayre PH, Lawson K, Bahnson HT, Sever ML, Radulovic S, Plaut M, Lack G; Immune Tolerance Network LEAP Study Team. Impact of peanut consumption in the LEAP Study: Feasibility, growth, and nutrition. J Allergy Clin Immunol. 2016 Oct;138(4):1108-1118. doi: 10.1016/j.jaci.2016.04.016. Epub 2016 Jun 10.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: May 23, 2006
• First Submitted That Met QC Criteria: May 23, 2006
• First Posted (ESTIMATE): May 25, 2006

Study Record Updates

• Last Update Posted (ACTUAL): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: eczema; children; infants; allergy; peanut; egg allergy; anaphylaxis; allergic reaction; allergies; peanut allergy
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Dermatitis; Skin Diseases, Eczematous; Hypersensitivity; Egg Hypersensitivity; Eczema; Food Hypersensitivity
• Other Study ID Numbers: DAIT ITN032AD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The plan is to share data in: 1.)ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools that are available to researchers who register online; and 2.)TrialShare, a clinical trials research portal of the Immune Tolerance Network (ITN).
• IPD Sharing Time Frame: Data sets et al of the manuscript are available to the public in TrialShare.
• IPD Sharing Access Criteria: The study ID in TrialShare is LEAP ITN032AD. Access is available to the public.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: SDY660
   Information comments: ImmPort study identifier is SDY660
2. Study summary, -design, -adverse event(s), -demographics, -study files
   Information identifier: SDY660
   Information comments: ImmPort study identifier is SDY660
3. Individual Participant Data Set
   Information identifier: LEAP (ITN032AD)
   Information comments: TrialShare study identifier is LEAP (ITN032AD)
4. Overview, Date & Reports, Manuscripts et al.
   Information identifier: LEAP (ITN032AD)
   Information comments: TrialShare study identifier is LEAP (ITN032AD)