Kinetics of Nasal Cytokine Responses to Mechanical Stimulation

NCT04878237 | Completed

• 1 other identifier: MUViennaAstra2021
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

IgE-associated allergy is a hypersensitivity disease affecting more than 40% of the population in industrialised countries. Recently the kinetics of change of clinical and immunological parameters (e.g. nasal blockage and cytokine profiles) in response to allergen exposure have been described. Additionally through recent placebo controlled studies it has become clear that the response of certain cytokines can not only be triggered by allergen exposure but also mechanically e.g through the insertion of nasal swabs for collection of cytokines. However it is not clear to what extent the mechanically triggered cytokine responses may differ between healthy, allergic and asthmatic patients who have been shown to have different cytokine profiles in their nasal secretions and varying impairment of their respiratory epithelium. As collection devices for nasal secretions are frequently used in clinical studies, the investigators aim to assess the impact of mechanical stimulation by frequent cytokine sampling on the cytokine profile.

Conditions

Allergic Rhinitis Due to Grass Pollen; Allergic Asthma

Outcome Measures

Primary Outcomes (1)

• Nasal cytokine responses to repeated mechanical stimulation in allergics, non allergics and asthmatics.

  The change in concentrations over time of a panel of relevant cytokines in Th2 immune responses e.g. IL-4, 5, 13 (all in pg/ml) will be measured using MSD multiplex assays to map responses to mechanical stimulation of the nasal mucosa.

  1 Year

Secondary Outcomes (3)

• Changes in nasal airflow as a result of repeated nasal sampling

  1 Year

• Changes in nasal symptoms using the a validated nasal symptom scoring system

  1 Year

• Defining differences in baseline and post sampling cytokine nasal mRNA levels

  1 Year

Study Arms (3)

Non Allergic Patients

PLACEBO COMPARATOR

Other: Nasal Secretion Sampling

Allergic Asthma Patients

ACTIVE COMPARATOR

Allergy to Grass Pollen

Other: Nasal Secretion Sampling

Allergic Rhinitis Patients

ACTIVE COMPARATOR

Allergy to Grass Pollen

Other: Nasal Secretion Sampling

Interventions

Nasal Secretion Sampling OTHER

Nasal specimen collection will be performed at all visits. For every visit specimens will be collected using nasosorption FXi/PU (containing a synthetic absorptive matrix (SAM)), or a 10 cm-long plastic curette (nasosorption devices from Hunt Developments, UK) (Curette devices from Arlington Scientific, USA)

Allergic Asthma Patients; Allergic Rhinitis Patients; Non Allergic Patients

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All groups
• Male or female
• to 50 years of age
• Willingness to comply with the study protocol and written informed consent
• Subjects must have a standard health care insurance
• Subjects must be available during the study period to complete all treatments and assessments
• Allergic Rhinitis
• Moderate to severe allergic rhinitis to grass pollen for at least two seasons according to medical history
• Skin prick test positive to grass pollen extract
• Blood ImmunoCAP sensitisation to grass pollen (\>0.35 kU/L grass pollen extract specific IgE or higher as determined by UniCAP-FEIA)
• No history of Asthma
• Allergic Asthma
• Clinical history of asthma
• Spirometry reversibility or PC20 methacholine/histamine \<8mg
• Skin prick test positive to grass extract

You may not qualify if:

• Older than 50 or younger than 18 years
• Active smoker
• History of anaphylaxis
• Any severe chronic, malignant or general disease
• Treatment with systemic or topical (intranasal, inhaled, external) corticosteroids within the previous 2 months before the start of the study
• Treatment with antihistamines 3 days prior to the screening visit of the study
• Treatment with other immunosuppressant drugs within the previous 6 months prior to the start of the study
• Arterial hypertension or use of anti-hypertensive therapy, including beta-blockers
• Contra-indications to skin prick testing such as: skin inflammation in the test area, urticaria facticia
• Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method
• A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude
• Participation in another clinical trial within one month prior to the study; however participation during the previous month solely in the form of blood donation and/or without other interventions will be accepted
• Known alcohol or drug addiction or abuse
• Risk of non-compliance with the study procedure
• Previous immunotherapy with grass pollen

Sponsors & Collaborators

• Medical University of Vienna: lead
• AstraZeneca: collaborator

Study Sites (1)

8H1.02, ENT Lab, Department of Otorhinolaryngology, Vienna General Hospital

Vienna, 1090, Austria

Location

Related Publications (8)

• Weinberg EG. The Wao White Book on Allergy 2011-2012. Curr Allergy Clin Im. 2011;24(3):156-7.

  BACKGROUND

• Bischoff SC. Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol. 2007 Feb;7(2):93-104. doi: 10.1038/nri2018.

  PMID: 17259966 BACKGROUND

• Valent P, Bettelheim P. The human basophil. Crit Rev Oncol Hematol. 1990;10(4):327-52. doi: 10.1016/1040-8428(90)90009-h. No abstract available.

  PMID: 2278641 BACKGROUND

• Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008 Jul 24;454(7203):445-54. doi: 10.1038/nature07204.

  PMID: 18650915 BACKGROUND

• Leaker BR, Malkov VA, Mogg R, Ruddy MK, Nicholson GC, Tan AJ, Tribouley C, Chen G, De Lepeleire I, Calder NA, Chung H, Lavender P, Carayannopoulos LN, Hansel TT. The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1beta), and complement. Mucosal Immunol. 2017 Mar;10(2):408-420. doi: 10.1038/mi.2016.74. Epub 2016 Sep 28.

  PMID: 27677865 BACKGROUND

• Thwaites RS, Gunawardana NC, Broich V, Mann EH, Ahnstrom J, Campbell GA, Lindsley S, Singh N, Tunstall T, Lane DA, Openshaw PJ, Hawrylowicz CM, Hansel TT. Biphasic activation of complement and fibrinolysis during the human nasal allergic response. J Allergy Clin Immunol. 2018 May;141(5):1892-1895.e6. doi: 10.1016/j.jaci.2018.01.022. Epub 2018 Feb 7. No abstract available.

  PMID: 29427640 BACKGROUND

• Downie SR, Andersson M, Rimmer J, Leuppi JD, Xuan W, Akerlund A, Peat JK, Salome CM. Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects. Allergy. 2004 Apr;59(4):406-14. doi: 10.1111/j.1398-9995.2003.00420.x.

  PMID: 15005764 BACKGROUND

• Boelke G, Berger U, Bergmann KC, Bindslev-Jensen C, Bousquet J, Gildemeister J, Jutel M, Pfaar O, Sehlinger T, Zuberbier T. Peak nasal inspiratory flow as outcome for provocation studies in allergen exposure chambers: a GA2LEN study. Clin Transl Allergy. 2017 Sep 17;7:33. doi: 10.1186/s13601-017-0169-4. eCollection 2017.

  PMID: 28932387 BACKGROUND

Study Officials

• Sven Schneider, MD

  Attending ENT Specialist

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: May 7, 2021
• Study Start: March 25, 2021
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: August 13, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)