Follow up of LEAP Participants and Their Families

• ClinicalTrials.gov Identifier: NCT03546413
• Recruitment Status: Recruiting
• First Posted: June 6, 2018
• Last Update Posted: July 12, 2019
• 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:

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 December of 2020. This will allow for the enrollment of former LEAP participants aged 12 years.:

• The enrollment phase will be 69 weeks (1 year, 4.25 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. The visit must be completed within 8 weeks of enrollment.

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
• Estimated Enrollment: 2321 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
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: December 31, 2020

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. Number of Participants with Peanut Allergy at 144 months of Age: LEAP Consumers versus LEAP Avoiders [ Time Frame: At age 144 months ]
   The number of participants with peanut allergy will be compared. Peanut oral food challenges will be conducted during their study visit as unblinded open challenges. This comparison will evaluate whether the consumption of peanut starting in infancy induces long-lasting tolerance to peanut. (Reference: NCT00329784)
2. Number of Participants with Peanut Sensitization Among Younger Siblings of LEAP Consumers versus LEAP Avoiders [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]

   Peanut sensitization will be defined as:

   • Sp-IgE ≥0.35kU/L or
   • Sp-IgE to individual peanut component Ara h2 ≥0.1kU/L, or
   • Skin prick test to peanut ≥3mm

   (Reference: NCT00329784)

Secondary Outcome Measures :

1. Comparison in Peanut Consumption By Participants: LEAP Study Cohort versus Siblings Cohort [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]

   A comparison in the amount of peanut consumption by participants will be assessed, using a dietary assessment.

   Method: A dietary history will be obtained using a food diary that captures typical food consumption.

2. Number of Participants with Specific Skin-Prick Test Greater than or Equal to 3 mm [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]
   Participants will be assessed for potential allergy to select food allergens. Participants will be classified as having a specific sensitivity if a skin prick containing the allergen produces a wheal size measuring ≥ 3 mm.
3. Number of Participants With Food Specific IgE Greater Than or Equal to 0.35 kU/L [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]
   Participants will be classified as having a specific food sensitivity if serum blood test results show specific IgE levels ≥0.35 kU/L for select ingested allergens.
4. Number of Participants with Asthma [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]

   The number of participants with asthma, within and across cohorts, will be determined using standard methodology. Definition: 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, or
   • occurred during the night, during early morning, or upon exercising in the intervals between exacerbations at any time in the previous 12 months.
5. Number of Participants with Rhinitis [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]
   The number of participants with rhinitis, within and across cohorts, will be evaluated 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).
6. Number of Participants with Eczema Using the SCORAD [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]
   The number of participants with eczema, within and across cohorts, will be evaluated using standard methodology. Participants will be assessed for eczema using a modified Scoring Atopic Dermatitis System (SCORAD). 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.
7. Number of Participants Among Younger Siblings with Peanut Allergy [ Time Frame: Through participant study completion, an average of 1 day (maximum of 2 days, the 2nd day within 8 weeks of enrollment) ]

   The number of siblings that are peanut allergic will be compared: younger siblings of LEAP consumers versus younger siblings of LEAP avoiders.

   Peanut oral food challenges will be conducted during their study visit as unblinded open challenges.

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: 12 Years 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;
• 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;
• Resident in same home as LEAP participant for at least one year during LEAP study;
• 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; Recruiting

London, United Kingdom, SE1 7EH

Contact: Richard Cleaver 020 7188 9521 Richard.cleaver@gstt.nhs.uk

Principal Investigator: Gideon Lack, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

• Study Chair: Gideon Lack; Evelina Children's Hospital Guy's and St. Thomas' NHS Foundation Trust, Paediatric Allergy Clinical Trials Unit Level 1,

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 )
• First Posted: June 6, 2018
• Last Update Posted: July 12, 2019
• Last Verified: July 2019

• 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