Follow up of LEAP Participants and Their Families

• ClinicalTrials.gov Identifier: NCT03546413
• Recruitment Status: Completed
• First Posted: June 6, 2018
• Last Update Posted: December 5, 2022
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN); PPD
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

This prospective, cross-sectional study is designed to improve understanding of how early-life introduction of peanuts may promote the development of tolerance at 12 years of age and will serve as an additional safety evaluation of this nutritional intervention.

Condition or disease
Peanut Allergy

Detailed Description:

Background: Food allergies and peanut allergy (PA) are becoming increasingly common conditions and are an important public health concern. Dietary avoidance of peanut in early life has been recommended in many countries. However, there is evidence that the prevalence of PA is decreased in countries where children are fed peanut beginning at an early age.

The LEAP (Learning Early About Peanut allergy) Study (Protocol ITN032AD, NCT00329784) demonstrated that the early consumption of peanut in high-risk infants successfully reduced the prevalence of peanut allergy at five years of age when compared to peanut avoidance. The LEAP-On Study (Protocol ITN049AD, NCT01366846) was a follow-on study to LEAP and investigated whether children who consumed peanut remained protected against developing peanut allergy even after cessation of peanut consumption for a period of 12 months. The key finding of the LEAP studies is that early introduction and consumption of peanut until 60 months of age causes a reduction in peanut allergy that persists at 72 months of age, even with a 12-month period of avoidance.

This LEAP Trio cohort study:

This longer-term follow-up of the study participants will assess whether the benefits of regular early-life peanut consumption are maintained over many years when followed by consumption of peanut ad lib, or as much and as often as desired.

The three cohorts will include LEAP:

• Participants (NCT00329784, NCT01366846)
• Siblings and
• Parents

The study will begin in 2018 with data collection continuing until August 31, 2022. This will allow for the enrollment of former LEAP participants aged 12 years.:

• The enrollment phase will be 234 weeks (4 years, 6 months).

  --The LEAP siblings and parents cohorts will be enrolled concurrently with the LEAP participant cohort.

• Study participation phase will be 1 visit; however, more than one clinic appointment may be required to complete all assessments.

Participant assessments will include general medical, -dietary, -allergy (including but not limited to oral peanut food challenges for former LEAP participants and their siblings), and mechanistic assessments (involving the collection of biological specimens, a blood draw, skin prick testing, as examples, to explore hypotheses related to potential mechanisms of peanut allergy).

Study Design

• Study Type: Observational
• Actual Enrollment: 1868 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Follow up of Learning Early About Peanut Allergy (LEAP) Participants and Their Families: LEAP Trio (ITN070AD)
• Actual Study Start Date: July 5, 2018
• Actual Primary Completion Date: August 31, 2022
• Actual Study Completion Date: August 31, 2022

Groups and Cohorts

Group/Cohort
LEAP Participants; LEAP participants are followed during an extended period of ad-libitum peanut consumption and then assessed for peanut allergy and other allergic outcomes. Target accrual is 630.
LEAP Siblings; LEAP participant siblings will be randomly assigned to the intervention or control group based on the allocation of their LEAP participants sibling.Target accrual is 746.
LEAP Parents; Any parent of a child who enrolled in the LEAP study. Target accrual is 945.

Outcome Measures

Primary Outcome Measures :

1. Percentage of LEAP Participants with Peanut Allergy at 144 months of Age [ Time Frame: At age 144 months ]
   Peanut allergy status will be determined by available data collected at enrollment in peanut oral food challenge, peanut consumption questionnaire, skin prick test to peanut, specific-IgE to peanut and specific-IgE to individual peanut components Ara h1, Ara h2 and Ara h3. This comparison will evaluate whether the consumption of peanut starting in infancy induces long-lasting tolerance to peanut. (Reference: NCT00329784)
2. Percentage of Participants with Peanut Sensitization Among Younger Siblings of LEAP Participants who Resided in the Home of the LEAP Participant on or before LEAP Visit 60 [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]

   Peanut sensitization will be defined as:

   Specific-IgE ≥0.35kU/L or Specific-IgE to individual peanut component Ara h2 ≥0.1kU/L, or Skin prick test wheal to peanut ≥3mm (Reference: NCT00329784)

Secondary Outcome Measures :

1. Average weekly peanut protein consumption prior to Visit 144 for LEAP Participants [ Time Frame: 4 weeks prior to Visit 144 ]
   Peanut consumption questionnaire responses to the question for average peanut protein consumption per week for the 4 weeks prior to Visit 144 will be used in the analysis.
2. Peanut skin prick test wheal size for LEAP Participants [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Participants will be assessed for potential peanut allergy, select food allergens, and select aeroallergens.
3. Peanut specific-IgE measurements for the LEAP Participants [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Participants will have blood draws to assess specific-IgE measurements to peanut, select food allergens and select aeroallergens
4. SCORAD score for the eczema severity in LEAP Participants [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Eczema severity will be assessed using a modified Scoring Atopic Dermatitis (SCORAD) assessment. 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
5. Percentage of LEAP Participants with Eczema [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Participants will be classified as having eczema using standard methodology. Participants will be assessed for eczema using a modified Scoring Atopic Dermatitis System (SCORAD) and using participant report of a history of 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.
6. Percentage of LEAP Participants with Asthma [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]

   Participants will be classified as having asthma if they meet at least one of the following definitions:

   1. if the participant has a history of cough, wheeze, or shortness of breath that was responsive to therapy with bronchodilators on two or more occasions in the previous 24 months, required one visit to a physician in the previous 24 months, and occurred during the night, during early morning, or upon exercising in the intervals between exacerbations at any time in the previous 12 months.
   2. participant report of an asthma diagnosis with current use of asthma medications (short-acting beta-agonist or controller)
   3. participant report of transient wheeze on exposure to a suspected allergen with confirmatory allergy tests.
7. Percentage of LEAP Participants with Rhinitis [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]

   Participants will be classified as having rhinitis using standard methodology. Two types of rhinitis will be assessed: perennial rhinoconjunctivitis and seasonal rhinoconjunctivitis. Definition: Participants will be considered to have either type of rhinitis if they demonstrate 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). Sensitization to the relevant allergen will be defined as:

   1. Allergen specific IgE ≥ 0.35 kU/L, or
   2. Skin prick test wheal size to allergen ≥ 3 mm.
8. Percentage of LEAP Younger Siblings with Peanut Allergy [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Peanut allergy status will be determined by available data collected at enrollment in peanut oral food challenge, peanut consumption questionnaire, skin prick test to peanut, specific-IgE to peanut and specific-IgE to individual peanut components Ara h1, Ara h2 and Ara h3.
9. Percentage of LEAP Participants with at least one peanut-related adverse event [ Time Frame: At enrollment. Additional visits may be performed to complete collection of all assessments ]
   Peanut-related adverse events will be reported from reactions experienced during or within 30 days after the peanut oral food challenge.

Biospecimen Retention:   Samples With DNA

Blood samples will be collected for peripheral blood mononuclear cell (PBMC) isolation and sent to the Immune Tolerance Network (ITN) designated core laboratory for processing using ITN approved standard operating procedures (SOPs) for PBMC separation and aliquoting. These cells will be available for future studies such as immunosequencing and functional studies when remaining cell numbers are sufficient to make these assays technically feasible. In the study, DNA will be collected for genetic analyses. Stool will be collected for possible future analysis.

Eligibility Criteria

• Ages Eligible for Study: 0 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

• Original Learning Early About Peanut (LEAP) allergy study participants (NCT00329784): at high risk for peanut allergy, given the presence of severe eczema, egg allergy, or both
• Siblings of LEAP participants
• Parents of LEAP participants

Criteria

Inclusion Criteria:

Inclusion Criteria - LEAP Participants:

• Participation in LEAP;
• At least 9.5 years of age
• Willingness to participate in at least one study data collection (i.e. questionnaire, skin pricking testing, or blood draw) procedure; and
• Assent by child and informed consent by parent or legal guardian.

Inclusion Criteria - LEAP Siblings:

• Sibling of LEAP participant;
• Willingness to participate in at least one study data collection (i.e. questionnaire, skin pricking testing, or blood draw); and
• Assent by child and informed consent by parent or legal guardian if child is younger than 16; siblings aged 16 and over will provide their own consent.

Inclusion Criteria - LEAP Parents:

• Biological parent of LEAP participant;
• Willingness to participate in at least one study data collection (i.e. questionnaire, skin pricking testing, or blood draw); and
• Informed consent (for participants only returning a Questionnaire, informed consent will be implied).

Exclusion Criteria:

• There are no exclusion criteria for LEAP Participants, LEAP Siblings, LEAP Parents

Contacts and Locations

Locations

United Kingdom

Evelina London Children's Hospital

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

PPD

Investigators

• Study Chair: Gideon Lack, MD; Evelina Children's Hospital, Guy's and St. Thomas's NHS Foundation Trust

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) 

Division of Allergy, Immunology, and Transplantation (DAIT) 

Immune Tolerance Network (ITN) 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03546413
• Other Study ID Numbers: DAIT ITN070AD; LEAP Trio ( Other Identifier: Immune Tolerance Network ); NIAID CRMS ID#: 38498 ( Other Identifier: DAIT NIAID )
• First Posted: June 6, 2018
• Last Update Posted: December 5, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.
• URL: https://www.immport.org/home

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

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

food; peanut; allergy; prevention

Additional relevant MeSH terms:

Hypersensitivity; Peanut Hypersensitivity; Immune System Diseases; Nut and Peanut Hypersensitivity; Food Hypersensitivity; Hypersensitivity, Immediate