Contribution of Nasal IgE Production to the Boost of Systemic Allergen-specific IgE Upon Nasal Allergen Contact

NCT05042830 | Recruiting

• 1 other identifier: IgE21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

IgE-associated allergies are consistently on the rise forming an enormous wellbeing concern and affecting about 25% of the population around the world, with main prevalence in developed nations. Birch pollen is one important allergen driving allergic conjunctivitis and rhinitis. The characteristics and location IgE producing cells in the nose and their contribution to the subsequent increase in allergen-specific IgE levels in the serum have so far poorly been investigated. Understanding these mechanisms is critical for the development of new therapeutic approaches and is thus the aim of the proposed study. Thus, the investigators plan to conduct a two-armed study of a randomized placebo-controlled double-blind nasal allergen provocation where 30 patients will be provoked with birch pollen extract (n=20) or placebo (n=10) out of the birch pollen season (October) and follow them closely for up to 4 months. Therefore, the objective of this study is to investigate the localization and characteristics of IgE producing cells in the nasal mucosa contributing to the allergen-induced boosts of specific serum IgE upon natural and controlled nasal allergen exposure.

Conditions

Allergy

Keywords

Hypersensitivity; Immunological Diseases

Outcome Measures

Primary Outcomes (1)

• Quantification of IgE producing cells

  Quantification of the number of IgE producing cells in blood and nasal biopsies (Number of IgE producing cells of total cells) by flow cytometry and microscopy

  3 years

Study Arms (2)

Active group

ACTIVE COMPARATOR

Birch allergic subjects receiving birch pollen extract challenge

Procedure: Blood sampling; Procedure: Nasal biopsies; Biological: Nasal specimen collection; Procedure: Mucosal RNA sampling; Procedure: Intranasal challenge; Procedure: Skin prick test; Procedure: Peak Nasal Inspiratory Flow (PNIF); Biological: Pregnancy test

Control group

PLACEBO COMPARATOR

Birch allergic subjects receiving saline

Procedure: Blood sampling; Procedure: Nasal biopsies; Biological: Nasal specimen collection; Procedure: Mucosal RNA sampling; Procedure: Intranasal challenge; Procedure: Skin prick test; Procedure: Peak Nasal Inspiratory Flow (PNIF); Biological: Pregnancy test

Interventions

Blood sampling PROCEDURE

Blood samples will be taken by puncture of the antecubital vein for peripheral blood mononuclear cells (PBMCs) isolation, cytokines measurement, and flow cytometry analysis

Active group; Control group

Nasal biopsies PROCEDURE

Nasal biopsies will be taken from the lower fringe of the inferior turbinate, approximately 1-2cm from the anterior curved edge for RNA sequencing and confocal microscopy staining

Active group; Control group

Nasal specimen collection BIOLOGICAL

Nasal specimen collection will be conducted. Nasosorption FXi/PU (containing a synthetic absorptive matrix (SAM)) will be obtained.

Active group; Control group

Mucosal RNA sampling PROCEDURE

A 10 cm nasal curette will be used (Rhino-Probe, Arlington Scientific, USA). The curette is brought to lie against the mid-inferior portion of the inferior turbinate under direct visualisation. The curette is rubbed against the mucosal surface, going outwards. To ensure successful sample acquisition, this motion will be repeated 2-3 times

Active group; Control group

Intranasal challenge PROCEDURE

The extract of birch pollen (Allergopharma, Vienna, Austria) will be freshly diluted in a 0.9 percent sterile sodium chloride solution and administered by means of a metered pump. The allergen will be administered supplying 15 μl per puff to both nostrils. Azelastine nasal spray or desloratadine 5mg will be given if the patient suffers from nasal or eye symptoms after the challenge. Equivalent amount of saline without allergens will be given to the control group.

Active group; Control group

Skin prick test PROCEDURE

In order to evaluate the patient's sensitization profile at the screening visit, a regular skin prick test will be conducted with commercial birch pollen extract and a panel of allergens used in routine diagnosis in the allergy clinic of the ear, nose, and throat (ENT) department. Titrated skin prick test: Titrated skin prick test (SPT) to birch pollen extract is conducted by using increasing dilutions up to 1:100 000. As a result, it is possible to determine the lowest concentration that leads in a skin reaction.

Active group; Control group

Peak Nasal Inspiratory Flow (PNIF) PROCEDURE

The functionality and convenience of the PNIF presents a rare opportunity to rapidly obtain objective measurements of nasal peak inspiratory flow. It was also validated during other nasal allergen challenge as a study tool

Active group; Control group

Pregnancy test BIOLOGICAL

In female patients, a regular urine pregnancy test will rule out pregnancy. The test will be conducted at the screening visit before the first skin prick test and then once a month afterwards.

Active group; Control group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Birch pollen sensitized subjects
• Moderate to severe allergic rhinitis to birch pollen allergen for at least two seasons according to their medical history
• Sensitization to Bet v 1 (Bet v 1 specific IgE: 3.5 kU/L or higher as specified by UniCAP-FEIA)
• CD203c or CD63 upregulation upon challenge with Bet v 1 in flow cytometric basophil activation tests (≥20% upregulation of CD63 or CD203c upon Bet v 1 stimulation in comparison with unstimulated controls as measured by flow cytometry)
• Willingness to follow the protocol.
• Written informed consent
• Standard healthcare insurance
• Subjects should be available during the entire study period

You may not qualify if:

• Evidence of acute, chronic, malignant or general diseases- assessed by asking the patient (e.g. Did you suffer or are you currently suffering from any malignant or generalised disease? Did you suffer or are you currently suffering from any chronic disease? Did you have any acute disease in the past two weeks?).
• A History of anaphylaxis.
• Utilization of leukotriene modifiers.
• Utilization of long-acting antihistamines.
• Chronic or intermittent use of oral, inhaled, intramuscular, intravenous, and potent topical corticosteroids.
• Nasal polyps, history of chronic sinusitis or considerable deviation of the nasal septum
• Rhinitis secondary to other causes.
• Contra-indications to skin prick testing, for example, skin irritation in the test area and urticaria factitia.
• Cardiovascular diseases or anti-hypertensive therapy and beta-blockers.
• Any disruption of coagulation system through medication or known clotting disorders
• Prophylactic aspirin therapy
• Chronic use of additional medications that would affect assessment and the results of the study (e.g., tricyclic antidepressants that block both H1 and H2 receptors)
• Pregnant or breastfeeding females.
• Actual disability that would influence subject's ability to participate in the study.
• History of mental illness, intellectual deficiency, drug or alcohol abuse

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

RECRUITING

Related Publications (24)

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MeSH Terms

Conditions

Hypersensitivity; Immune System Diseases

Interventions

Blood Specimen Collection; Patch Tests; Pregnancy Tests

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Skin Tests; Immunologic Tests; Immunologic Techniques; Diagnostic Techniques, Obstetrical and Gynecological

Study Officials

• Sven Schneider, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sven Schneider, MD

CONTACT

+4314040034380; sven.schneider@meduniwien.ac.at

Julia Eckl-Dorna, MD, PhD

CONTACT

+4314040034380; julia.eckl-dorna@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 13, 2021
• Study Start: November 11, 2021
• Primary Completion: January 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 7, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)