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

Allergic Rhinitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02461797
• Other study ID #: biopsystudy
• Status: Completed
• Phase: N/A
• First received: April 27, 2015
• Last updated: May 29, 2015
• Start date: August 2014
• Est. completion date: March 2015

Study information

• Verified date: April 2015
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. 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

2. Age > 18 and < 60 years.

3. Possibility to give reliable information and written informed consent

4. 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:

1. No common cold in the last 4 weeks

2. Patients on prolonged use of decongestive nose sprays, suffering from so-called rhinitis medicamentosa

3. 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.

4. 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

5. Patients on immunotherapy (IT) for house dust mite (HDM) or with history of IT for HDM

6. 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

7. Patients being enrolled in other clinical trials

8. Pregnancy or breastfeeding

9. Malignancies or severe comorbidity

10. Contra-indication for local anesthesia with cocaine 5%

11. Smoking

12. Use of anticoagulation medication

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

1. Absence of nasal symptoms

2. Negative history of respiratory allergy

3. Negative skin prick test (SPT) results

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Allergic Rhinitis
• Rhinitis

Intervention

Other:
• healthy controls
biopsy of nasal mucosa for healthy controls
• AR patients without medication
biopsy of nasal mucosa for allergic rhinitis patients without allergy medication
• AR patients with use of nasal corticoid spray
biopsy of nasal mucosa for allergic rhinitis patients with use of nasal corticoid spray

Locations

Country	Name	City	State
Belgium	ORL	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Oxcm².	every 30 min over 2 hours	No
Primary	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.	every 30 min over 2 h	No