Clinical trial NCT00329784: Promoting Tolerance to Peanut in High-Risk Children
Official title: Induction of Tolerance Through Early Introduction of Peanut in High-Risk Children (ITN032AD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eczema
Egg Allergy
Food Allergy
Keywords: peanut allergy
egg allergy
eczema
peanut
allergy
allergies
allergic reaction
anaphylaxis
infants
children
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2006-05-25
Enrollment: 640
Sex: ALL
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Peanut Allergy at 60 Months of Age - by Skin Prick Test Stratum
timeFrame: 60 months
measure: Number of Participants With Peanut Allergy at 60 Months of Age - Both Strata Combined
timeFrame: 60 months
Secondary outcomes:
measure: SCORAD at 60 Months
timeFrame: 60 months
measure: Number of Participants With Asthma at 60 Months
timeFrame: 60 months
measure: Number of Participants With Rhinitis at 60 Months
timeFrame: 60 months
measure: Number of Participants With Specific Skin Prick Test Greater Than or Equal to 3mm
timeFrame: 60 months
measure: Number of Participants With Food Specific IgE Greater Than or Equal to 0.35 kU/L
timeFrame: 60 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust
state: England
Study officials:
affiliation: Imperial College, St. Mary's Hospital
name: Gideon Lack, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.