The Clinical Impact of the Basophil Activation Test to Diagnose Food Allergy

NCT ID: NCT05309772

Last Updated: 2023-09-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

398 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-13

Study Completion Date

2025-07-31

Brief Summary

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The BAT Impact study is a prospective multicentre study in the UK using a biomarker-led study design to compare the incidence of adverse events (defined as allergic reactions during oral food challenges) in a randomized-controlled trial. Patients will either follow the standard-of-care (i.e. an oral food challenge in case of equivocal SPT/sIgE) or follow a basophil activation test (BAT)/mast cell activation test (MAT)-based strategy, i.e. patients with a positive BAT or MAT are dispensed of an oral food challenge (OFC) and patients with a negative BAT/MAT undergo an OFC.

Detailed Description

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Children aged 6 months to 15 years requiring an oral food challenge to one of the study foods (milk, egg, peanut, sesame or cashew nut) will be invited to participate in the study.

Eleven centres across the UK will be recruiting participants and perforning clinical procedures, such as skin prick testing and oral food challenges (OFC), as per standard clinical care.

Participants will be randomised 4:5 to either have the standard-of-care, i.e. oral food challenge to the suspected food, or take BAT (MAT if BAT inconclusive) into account to decide whether or not OFC will be required: if BAT/MAT is positive, food allergy will be confirmed without doing OFC; if BAT/MAT is negative, participants in the biomarker arm will undergo OFC.

The primary outcome is the proportion of positive OFC in the biomarker arm compared with the standard-of-care arm.

Secondary outcomes are: number of OFC, quality of life, anxiety and costs associated with the diagnostic work-up.

Conditions

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Food Allergy Food Allergy in Infants Food Allergy in Children Food Allergen Sensitisation Milk Allergy Egg Allergy Nut Allergy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will be randomised using a 4:5 allocation between standard-of-care/biomarker arms. Stratified randomisation will be adopted according to recruiting centre, using a web-based allocation system.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Biomarker arm

All participants will have blood taken to test for BAT/MAT. Participants with a positive BAT/MAT will dispense from oral food challenge (OFC).

Participants with negative or inconclusive BAT/MAT will undergo OFC.

Group Type EXPERIMENTAL

Basophil activation test (BAT)

Intervention Type DIAGNOSTIC_TEST

Basophils and mast cells are the key drivers of food allergic reactions and anaphylaxis to foods. The study team have developed new tests that measure the reaction of mast cells and basophils by flow cytometry following stimulation with allergen, the BAT and the MAT:

• BAT uses fresh whole blood from patients added to allergen and antibodies in a test tube. The tube containing the allergic cells are then analysed one by one to estimate how many and how much express activation markers on their surface, CD63 and CD203c.

MAT uses a human mast cell line (LAD2 cells) which are human mast cells grown in the laboratory to which patients' plasma is added in order to mimic the patients' own mast cells. Sensitised LAD2 cells are then stimulated with allergen or controls and analysed by flow cytometry to assess the expression of the activation marker CD63 on the cell surface, similar to what happens in the BAT. Results of MAT will be considered only in cases of non-responding basophils.

Oral food challenge (OFC)

Intervention Type DIAGNOSTIC_TEST

Consumption of the food suspected of causing an allergic reaction in a medically supervised environment, starting with small amounts and progressively increasing the dose at regular intervals up to a cumulative dose corresponding to an age-appropriate portion of the food.

Standard-of-care arm

All participants in the standard-of-care arm will have blood taken to test for BAT/MAT. Regardless of the result of BAT/MAT, all participants in this arm will undergo an oral food challenge, as per the current standard-of-care.

Group Type ACTIVE_COMPARATOR

Basophil activation test (BAT)

Intervention Type DIAGNOSTIC_TEST

Basophils and mast cells are the key drivers of food allergic reactions and anaphylaxis to foods. The study team have developed new tests that measure the reaction of mast cells and basophils by flow cytometry following stimulation with allergen, the BAT and the MAT:

• BAT uses fresh whole blood from patients added to allergen and antibodies in a test tube. The tube containing the allergic cells are then analysed one by one to estimate how many and how much express activation markers on their surface, CD63 and CD203c.

MAT uses a human mast cell line (LAD2 cells) which are human mast cells grown in the laboratory to which patients' plasma is added in order to mimic the patients' own mast cells. Sensitised LAD2 cells are then stimulated with allergen or controls and analysed by flow cytometry to assess the expression of the activation marker CD63 on the cell surface, similar to what happens in the BAT. Results of MAT will be considered only in cases of non-responding basophils.

Oral food challenge (OFC)

Intervention Type DIAGNOSTIC_TEST

Consumption of the food suspected of causing an allergic reaction in a medically supervised environment, starting with small amounts and progressively increasing the dose at regular intervals up to a cumulative dose corresponding to an age-appropriate portion of the food.

Interventions

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Basophil activation test (BAT)

Basophils and mast cells are the key drivers of food allergic reactions and anaphylaxis to foods. The study team have developed new tests that measure the reaction of mast cells and basophils by flow cytometry following stimulation with allergen, the BAT and the MAT:

• BAT uses fresh whole blood from patients added to allergen and antibodies in a test tube. The tube containing the allergic cells are then analysed one by one to estimate how many and how much express activation markers on their surface, CD63 and CD203c.

MAT uses a human mast cell line (LAD2 cells) which are human mast cells grown in the laboratory to which patients' plasma is added in order to mimic the patients' own mast cells. Sensitised LAD2 cells are then stimulated with allergen or controls and analysed by flow cytometry to assess the expression of the activation marker CD63 on the cell surface, similar to what happens in the BAT. Results of MAT will be considered only in cases of non-responding basophils.

Intervention Type DIAGNOSTIC_TEST

Oral food challenge (OFC)

Consumption of the food suspected of causing an allergic reaction in a medically supervised environment, starting with small amounts and progressively increasing the dose at regular intervals up to a cumulative dose corresponding to an age-appropriate portion of the food.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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Mast cell activation test (MAT)

Eligibility Criteria

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Inclusion Criteria

* Children and young people aged 6 months to 15 years
* Suspected allergy to one of the study foods (peanut, cow's milk, egg, cashew, sesame) - defined as:

* history of clinical reaction or
* evidence of IgE sensitisation (SPT\>0mm and/or specific IgE\>=0.10 KU/L) to the respective food or
* reassessment for possible resolution of allergy to the specific food following previous diagnosis of food allergy
* Need for an oral food challengeOFC to the study food
* Oral food challengeOFC to reach amount of food protein in a typical portion size for child's age
* Consent from adults with parental responsibility and assent from children and young people in an age appropriate form.

Exclusion Criteria

* Clinically significant chronic illness other than atopic diseases;
* Previous history of severe life-threatening reaction to the suspected food with documented decrease in oxygen saturation (\<90%), hypotension (≥20% reduction in systolic blood pressure) and/or admission to intensive care;
* Unwillingness to comply with study procedures, namely to undergo a diagnostic food challenge;
* Contra-indication for diagnostic food challenge, namely:

* Uncontrolled atopic diseases (e.g. eczema, asthma, rhinitis);
* Chronic medical conditions that pose significant risk in the event of anaphylaxis or treatment of anaphylaxis (e.g. cardiac disease, severe lung disease, pregnancy, mastocytosis);
* Inability to discontinue medications that might interfere with assessment or safety (e.g. antihistamines, β-agonists, β-blockers, NSAIDs, ACE inhibitor, antacids);
* Recent (within 7-14 days) treatment with systemic steroids or prolonged high-dose systemic steroids or immunosuppressants;
* Undergoing treatment with omalizumab, food or inhalant allergen immunotherapy or other systemic immunomodulatory treatment;
* Inability to stop anti-histamines prior to SPT or OFC.
Minimum Eligible Age

6 Months

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sandwell & West Birmingham Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

NHS Lothian

OTHER_GOV

Sponsor Role collaborator

University Hospitals, Leicester

OTHER

Sponsor Role collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role collaborator

University College London Hospitals

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Sheffield Children's NHS Foundation Trust

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandra Santos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

King's College London

Locations

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Sandwell and West Birmingham Hospital

Birmingham, , United Kingdom

Site Status RECRUITING

Addenbrookes Hospital

Cambridge, , United Kingdom

Site Status NOT_YET_RECRUITING

Royal Hospital for Children and Young People

Edinburgh, , United Kingdom

Site Status NOT_YET_RECRUITING

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status RECRUITING

Evelina London Children's Hospital

London, , United Kingdom

Site Status RECRUITING

King's College Hospital

London, , United Kingdom

Site Status NOT_YET_RECRUITING

University College London Hospital

London, , United Kingdom

Site Status NOT_YET_RECRUITING

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status NOT_YET_RECRUITING

Great North Children's Hospital

Newcastle, , United Kingdom

Site Status NOT_YET_RECRUITING

Sheffield Children's Hospital

Sheffield, , United Kingdom

Site Status NOT_YET_RECRUITING

University Hospital Southampton

Southampton, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Alexandra Santos, MD, PhD

Role: CONTACT

+44 (0) 20 7188 6424

Facility Contacts

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Professor Alexandra Santos

Role: primary

Other Identifiers

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IRAS 299511

Identifier Type: -

Identifier Source: org_study_id

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