Biomarkers in Food Allergy Diagnosis

NCT04604912 | Completed DMC

• 1 other identifier: APSIS
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 2

Brief Summary

Food allergy is a global burden, affecting patients, society as a whole and the economy. For most common food allergies, patients synthesize specific IgE-antibodies against harmless food proteins. Clinical phenotypes of food-allergic patients are highly diverse. Differences in medical symptoms (organs, severity, delay), threshold and cross-reactivity levels suggest variable underlying endotypes. The aim of this study is to identify phenotypic biomarkers for advanced stratification of food-allergic patients. Our study will consist of up to 50 participants (30 food-allergic, 20 tolerant), recruited in Luxembourg. Clinical samples will be collected before, during and after the event of a double-blind placebo-controlled food challenge for patients. Multi-omics analyses of blood (sera, peripheral blood mononuclear cell, basophils) and stool will allow a deeper understanding of the underlying immune mechanisms, including allergen metabolism aspects, as well as the functional gut microbiome. Deciphering these basic aspects during the present pilot study is expected to pave the way towards novel personalized medicine approaches for diagnosing and treating of food-allergic individuals. This study is a cooperation project between the Centre Hospitalier de Luxembourg (CHL), the Luxemburg Institute of Health (LIH), the University of Luxembourg and the Integrated Biobank of Luxemburg (IBBL).

Conditions

Allergy;Food

Keywords

Peanut allergy; Active peptides; Oral food challenge; Immune cell phenotyping; Microbiome

Outcome Measures

Primary Outcomes (5)

• Change in peripheral allergen peptides (serum samples) across food allergen uptake

  Abundance of allergen peptides as detected through mass spectrometry. Main comparison will be on two study arms, food-allergic patients versus healthy controls

  Samples analyzed through study completion, an average of 3 months

• Change in in-vitro basophil reactivity profiles (cells sampled before food challenge) using defined food allergen peptides across different peptides mixes and peptide concentrations

  Reactivity of effector cells by dose-dependent activation (%-CD63+ CCR3+basophils) and flow cytometry measurement. Main comparison will be within the group of food-allergic patients, aligning patients with high/low reactivity and high/low sensitivity of basophils.

  Samples analyzed through study completion, an average of 3 months

• Change of immune cell phenotypes across food allergen uptake

  Abundance and function of immune cells as detected through single-cell mass cytometry. Main comparison will be on two study arms, food-allergic patients versus healthy controls.

  Samples analyzed through study completion, an average of 3 months

• Change in Cytokine release

  Cytokine quantification through multiplex immunoassays. Main comparison will be on two study arms, food-allergic patients versus healthy controls.

  Samples analyzed through study completion, an average of 3 months

• Baseline characteristics of the functional gut microbiome in food-allergic patients

  DNA, RNA, protein and metabolite profiling using a multi-omics approach through 16S RNA sequencing, unbiased high resolution method of metagenomics shotgun sequencing and transcriptomic analysis (Illumina MiSeq \& NextSeq) as well as metabolomic analysis (gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry). In addition, microbial component analysis by antibody-specific immunoassays and flow cytometry. Main comparison will be on two study arms, food-allergic patients versus healthy controls.

  Samples analyzed through study completion, an average of 2 months

Study Arms (2)

Peanut-allergic patients' group

The aim is to include 30 patients with peanut allergy. Those patients will undergo diagnostic food challenges (incremental doses) while blood will be samples before, during and after the testing. The patients will receive standard of care during and after the challenge. Allergic symptoms will be treated according to established guidelines.

Control group

The aim is to include 20 control participants, 10 peanut-tolerant and 10 fish-tolerant individuals. Those participants will undergo diagnostic food challenges (incremental or single doses) while blood will be samples before, during and after the testing. Same safety measures will be applied for food challenges of control individuals, as for the allergic patients.

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Peanut-allergic individuals (N=30) and tolerant controls (N=20). Among the allergic patients, up to 10 allergic individuals of age 2-5 will be included.

You may qualify if:

• years
• male or female
• Allergic to peanut (assessed by anamnesis, skinreactivity testing, sera testing for specific IgE)
• Sign an Informed Consent
• Diagnostic food challenge scheduled

You may not qualify if:

• Significant co-morbidity
• Medical treatment by nonsteroidal anti-inflammatory drugs oraspirin, chronic treatment with beta-blockers,angiotensin-converting enzyme inhibitors, use ofantihistamines within 5 days of oral food challenge and oral corticosteroids within 14 days prior to the challenge
• Medical unfit for challenge (e.g : fever,unwell with intercurrent illness)
• Pregant women
• Unbalanced asthma
• Severe food-induced anaphylaxis
• For the control cohort :
• Adults
• male or female
• Sign an Informed Consent
• Tolerance to peanuts and fish (IgE-titer \< 0.10 kUA/L)
• Pregnancy
• Medical unfit for challenge (e.g : fever, unwell with intercurrent illness),
• Unbalanced asthma
• Treatment by nonsteroidal anti-inflammatory drugs or aspirin

Sponsors & Collaborators

• Luxembourg Institute of Health: lead
• Centre Hospitalier du Luxembourg: collaborator
• Odense University Hospital: collaborator
• Technical University of Munich: collaborator
• University of Luxembourg: collaborator
• Integrated Biobank of Luxembourg: collaborator

Study Sites (2)

Luxembourg Institute of Health

Esch-sur-Alzette, 4354, Luxembourg

Location

Centre Hospitalier Luxembourg

Luxembourg, 1210, Luxembourg

Location

Related Publications (5)

• Muraro A, Lemanske RF Jr, Castells M, Torres MJ, Khan D, Simon HU, Bindslev-Jensen C, Burks W, Poulsen LK, Sampson HA, Worm M, Nadeau KC. Precision medicine in allergic disease-food allergy, drug allergy, and anaphylaxis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology. Allergy. 2017 Jul;72(7):1006-1021. doi: 10.1111/all.13132. Epub 2017 Apr 12.

  PMID: 28122115 BACKGROUND

• Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, Aalberse RC, Agache I, Asero R, Ballmer-Weber B, Barber D, Beyer K, Biedermann T, Bilo MB, Blank S, Bohle B, Bosshard PP, Breiteneder H, Brough HA, Caraballo L, Caubet JC, Crameri R, Davies JM, Douladiris N, Ebisawa M, EIgenmann PA, Fernandez-Rivas M, Ferreira F, Gadermaier G, Glatz M, Hamilton RG, Hawranek T, Hellings P, Hoffmann-Sommergruber K, Jakob T, Jappe U, Jutel M, Kamath SD, Knol EF, Korosec P, Kuehn A, Lack G, Lopata AL, Makela M, Morisset M, Niederberger V, Nowak-Wegrzyn AH, Papadopoulos NG, Pastorello EA, Pauli G, Platts-Mills T, Posa D, Poulsen LK, Raulf M, Sastre J, Scala E, Schmid JM, Schmid-Grendelmeier P, van Hage M, van Ree R, Vieths S, Weber R, Wickman M, Muraro A, Ollert M. EAACI Molecular Allergology User's Guide. Pediatr Allergy Immunol. 2016 May;27 Suppl 23:1-250. doi: 10.1111/pai.12563.

  PMID: 27288833 BACKGROUND

• Bunyavanich S, Berin MC. Food allergy and the microbiome: Current understandings and future directions. J Allergy Clin Immunol. 2019 Dec;144(6):1468-1477. doi: 10.1016/j.jaci.2019.10.019.

  PMID: 31812181 BACKGROUND

• Costa J, Bavaro SL, Benede S, Diaz-Perales A, Bueno-Diaz C, Gelencser E, Klueber J, Larre C, Lozano-Ojalvo D, Lupi R, Mafra I, Mazzucchelli G, Molina E, Monaci L, Martin-Pedraza L, Piras C, Rodrigues PM, Roncada P, Schrama D, Cirkovic-Velickovic T, Verhoeckx K, Villa C, Kuehn A, Hoffmann-Sommergruber K, Holzhauser T. Are Physicochemical Properties Shaping the Allergenic Potency of Plant Allergens? Clin Rev Allergy Immunol. 2022 Feb;62(1):37-63. doi: 10.1007/s12016-020-08810-9.

  PMID: 32876924 BACKGROUND

• Jappe U and Kuehn A. Neues zu diagnostisch relevanten Einzelallergenen aus pflanzlichen und tierischen Nahrungsmittelallergenquellen. Allergologie 2016; 39: 425-438. doi: 10.5414/ALX01885.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood-derived samples (sera, plasma, peripheral blood mononuclear cell/PBMC) and stool will be collected

MeSH Terms

Conditions

Food Hypersensitivity; Peanut Hypersensitivity

Condition Hierarchy (Ancestors)

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

Study Officials

• Annette Kuehn, PhD

  Luxembourg Institute of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Day
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 27, 2020
• Study Start: September 1, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

LU (2)