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Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

Primary Purpose

Allergic Rhinitis

Status

Completed

Phase

Not Applicable

Locations

Belgium

Study Type

Interventional

Intervention

healthy controls

AR patients without medication

AR patients with use of nasal corticoid spray

About this trial

This is an interventional basic science trial for Allergic Rhinitis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients with an ARIA-based diagnosis of persistent moderate/severe AR (≥ 2 nasal symptoms suggestive of allergic rhinitis and positive skin prick tests to HDM (HAL Allergy, Leiden, The Netherlands), and with VAS score for total nasal symptoms of more than 5
Age > 18 and < 60 years.
Possibility to give reliable information and written informed consent
For AR group with nasal corticosteroid spray: Patients that use nasal corticosteroid spray for at least three weeks prior to the study, with a minimum application of two puffs per nostril once a day.

Exclusion Criteria:

No common cold in the last 4 weeks
Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa
A. For healthy controls and AR without use of nasal spray: Patients using other nasal or oral medication affecting nasal function, like nasal corticosteroids, anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study.
B. For AR group with use of nasal corticosteroid spray: Patients using other nasal or oral medication affecting nasal function, like anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study.
Nasal endoscopic evidence of rhinosinusitis w/wo NP or structural abnormalities such as clinically relevant septal deviation (septum reaching concha inferior or lateral nasal wall) or septal perforation
Patients on immunotherapy (IT) for house dust mite (HDM) or with history of IT for HDM
Patient with a psychiatric, addictive, or any disorder of which the investigators feel that this may compromise the ability to give truly informed consent for participation in this study or provide reliable information on the questionnaire
Patients being enrolled in other clinical trials
Pregnancy or breastfeeding
Malignancies or severe comorbidity
Contra-indication for local anesthesia with cocaine 5%
Smoking
Use of anticoagulation medication

Healthy controls will meet the same exclusion criteria, with additional inclusion criteria:

Absence of nasal symptoms
Negative history of respiratory allergy
Negative skin prick test (SPT) results

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

healthy controls

AR patients with use of nasal corticoid spray

AR patients without medication

Arm Description

biopsy of nasal mucosa healthy controls

biopsy of nasal mucosa allergic rhinitis to house dust mite with nasal corticosteroid spray

biopsy of nasal mucosa allergic rhinitis to house dust mite without any use of medication for symptom control

Outcomes

Primary Outcome Measures

change in Transepithelial electrical resistance (TEER)

Nasal biopsies will be mounted in modified 3 ml Ussing chambers. Experiments will be performed in open-circuit conditions. Transepithelial electrical resistance (TEER) will be calculated from the voltage deflections induced by bipolar constant-current pulses of 16 mA every 60 s with duration of 200 ms and will be recorded every 30 min over 2 h. The average of all time points of the 2 biopsy samples/patient will be used and will be presented as Ωxcm².

change in mucosal permeability

The paracellular probe, fluorescently labelled dextran 4 kDa (FD4) (2 mg/ml) will be used to determine the mucosal permeability. FD4 will be added to the mucosal compartment and serosal samples will be collected every 30 min over 2 h. The fluorescence level will be measured using a fluorescence reader. The average of time points 60, 90 and 120 min of the 2 biopsy samples/patient will be used to express mucosal permeability.

Secondary Outcome Measures

Full Information

NCT ID

NCT02461797

First Posted

April 27, 2015

Last Updated

May 29, 2015

Sponsor

Universitaire Ziekenhuizen KU Leuven

1. Study Identification

Unique Protocol Identification Number

NCT02461797

Brief Title

Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

Official Title

Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Completed

Study Start Date

August 2014 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitaire Ziekenhuizen KU Leuven

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Recently, a critical role in the development of allergic rhinitis (AR) has been attributed to the nasal epithelium. The airway epithelium forms a physical barrier, protecting the nasal mucosa and underlying organs from damage from contact with exogenous particles. The nasal epithelial barrier is primarily determined by the integrity of the airway epithelium, in which epithelial cells are connected to each other by complex network structures like tight junctions (TJs), ultimately sealing off the paracellular space. TJs consist of different transmembrane proteins including occludin, tricellulin, the claudin family, and junctional adhesion molecules. TJ form intercellular homodimers/heterodimers between neighboring cells. Scaffold adaptor proteins like cingulin and the zonula occludens family connect the transmembrane proteins to the actin cytoskeleton. Disturbed TJ function can facilitate the entrance of foreign pathogens and antigens into the submucosal layer, giving raise to allergic sensitization via increased access of allergens to the dendritic cells and/or inducing persistent inflammation via activation of mast cells and other inflammatory cells residing in the upper airways. Chronic disorders like allergic asthma, inflammatory bowel disease and atopic dermatitis have been linked to defective or altered TJ function. Recently, an impaired epithelial barrier function was found in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), suggesting changes in TJ arrangement in the nasal cavity. CRSwNP presents a similar inflammation of the sinonasal cavities as found in AR patients, i.e. a Th2 cytokine driven inflammation with tissue eosinophilia. Nevertheless, the role of TJs and its regulation has not been investigated in AR.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Allergic Rhinitis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

healthy controls

Arm Type

Other

Arm Description

biopsy of nasal mucosa healthy controls

Arm Title

AR patients with use of nasal corticoid spray

Arm Type

Other

Arm Description

biopsy of nasal mucosa allergic rhinitis to house dust mite with nasal corticosteroid spray

Arm Title

AR patients without medication

Arm Type

Other

Arm Description

biopsy of nasal mucosa allergic rhinitis to house dust mite without any use of medication for symptom control

Intervention Type

Other

Intervention Name(s)

healthy controls

Intervention Description

biopsy of nasal mucosa for healthy controls

Intervention Type

Other

Intervention Name(s)

AR patients without medication

Intervention Description

biopsy of nasal mucosa for allergic rhinitis patients without allergy medication

Intervention Type

Other

Intervention Name(s)

AR patients with use of nasal corticoid spray

Intervention Description

biopsy of nasal mucosa for allergic rhinitis patients with use of nasal corticoid spray

Primary Outcome Measure Information:

Title

change in Transepithelial electrical resistance (TEER)

Description

Time Frame

every 30 min over 2 hours

Title

change in mucosal permeability

Description

Time Frame

every 30 min over 2 h

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with an ARIA-based diagnosis of persistent moderate/severe AR (≥ 2 nasal symptoms suggestive of allergic rhinitis and positive skin prick tests to HDM (HAL Allergy, Leiden, The Netherlands), and with VAS score for total nasal symptoms of more than 5 Age > 18 and < 60 years. Possibility to give reliable information and written informed consent For AR group with nasal corticosteroid spray: Patients that use nasal corticosteroid spray for at least three weeks prior to the study, with a minimum application of two puffs per nostril once a day. Exclusion Criteria: No common cold in the last 4 weeks Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa A. For healthy controls and AR without use of nasal spray: Patients using other nasal or oral medication affecting nasal function, like nasal corticosteroids, anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study. B. For AR group with use of nasal corticosteroid spray: Patients using other nasal or oral medication affecting nasal function, like anticholinergics, cromoglycates, leukotriene antagonists, ACE inhibitors less than 4 weeks before start of the study. Nasal endoscopic evidence of rhinosinusitis w/wo NP or structural abnormalities such as clinically relevant septal deviation (septum reaching concha inferior or lateral nasal wall) or septal perforation Patients on immunotherapy (IT) for house dust mite (HDM) or with history of IT for HDM Patient with a psychiatric, addictive, or any disorder of which the investigators feel that this may compromise the ability to give truly informed consent for participation in this study or provide reliable information on the questionnaire Patients being enrolled in other clinical trials Pregnancy or breastfeeding Malignancies or severe comorbidity Contra-indication for local anesthesia with cocaine 5% Smoking Use of anticoagulation medication Healthy controls will meet the same exclusion criteria, with additional inclusion criteria: Absence of nasal symptoms Negative history of respiratory allergy Negative skin prick test (SPT) results

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Peter Hellings, MD PhD

Organizational Affiliation

UZ Leuven

Official's Role

Principal Investigator

Facility Information:

Facility Name

ORL

City

Leuven

State/Province

Vlaams-Brabant

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Citations:

PubMed Identifier

26846377

Citation

Steelant B, Farre R, Wawrzyniak P, Belmans J, Dekimpe E, Vanheel H, Van Gerven L, Kortekaas Krohn I, Bullens DMA, Ceuppens JL, Akdis CA, Boeckxstaens G, Seys SF, Hellings PW. Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. J Allergy Clin Immunol. 2016 Apr;137(4):1043-1053.e5. doi: 10.1016/j.jaci.2015.10.050. Epub 2016 Feb 2.

Results Reference

derived

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Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients

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