Allergic RhinitisNCT02461797
Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients
A study testing AR patients without medication and AR patients with use of nasal corticoid spray in people with Allergic Rhinitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Allergic Rhinitis
- What is being tested?
- AR patients without medication and AR patients with use of nasal corticoid spray
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteBelgium
- Study dates
- Aug 2014to Mar 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Allergic Rhinitis
- Being tested
- healthy controls, AR patients without medication, AR patients with use of nasal corticoid spray
- Medical subject headings
- Rhinitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
healthy controlsOther
biopsy of nasal mucosa for healthy controls
AR patients without medicationOther
biopsy of nasal mucosa for allergic rhinitis patients without allergy medication
AR patients with use of nasal corticoid sprayOther
biopsy of nasal mucosa for allergic rhinitis patients with use of nasal corticoid spray
| Study group | Role | What they receive |
|---|---|---|
| healthy controls | Other | biopsy of nasal mucosa healthy controls Receives: Other: healthy controls |
| AR patients with use of nasal corticoid spray | Other | biopsy of nasal mucosa allergic rhinitis to house dust mite with nasal corticosteroid spray Receives: Other: AR patients with use of nasal corticoid spray |
| AR patients without medication | Other | biopsy of nasal mucosa allergic rhinitis to house dust mite without any use of medication for symptom control Receives: Other: AR patients without medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: every 30 min over 2 hours
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.
Measured: every 30 min over 2 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study startAug 2014
- Primary completionMar 2015
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Allergic RhinitisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Hellings, MD PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461797
- Sponsor's protocol ID
- biopsystudy
- Status last verified
- Apr 2015
- First submitted
- 27 Apr 2015
- Last updated
- 3 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26846377
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Nasal Mucosal Permeability in Controls and House Dust Mite Allergic Rhinitis Patients
- ClinicalTrials.gov ID
- NCT02461797
- Acronym / sponsor ID
- biopsystudy
- Conditions
- Allergic Rhinitis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 3 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| healthy controls | Other | Other: healthy controlsbiopsy of nasal mucosa healthy controls |
| AR patients with use of nasal corticoid spray | Other | Other: AR patients with use of nasal corticoid spraybiopsy of nasal mucosa allergic rhinitis to house dust mite with nasal corticosteroid spray |
| AR patients without medication | Other | Other: AR patients without medicationbiopsy of nasal mucosa allergic rhinitis to house dust mite without any use of medication for symptom control |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| healthy controlsbiopsy of nasal mucosa for healthy controls | Other | healthy controls |
| AR patients without medicationbiopsy of nasal mucosa for allergic rhinitis patients without allergy medication | Other | AR patients without medication |
| AR patients with use of nasal corticoid spraybiopsy of nasal mucosa for allergic rhinitis patients with use of nasal corticoid spray | Other | AR patients with use of nasal corticoid spray |
Primary outcome
change in Transepithelial electrical resistance (TEER)
Time frame: every 30 min over 2 hours
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
Time frame: every 30 min over 2 h
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2015.
- Derived from this study: PubMed 26846377Steelant 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Hellings, MD PhD principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AR patients without medication and AR patients with use of nasal corticoid spray in people with Allergic Rhinitis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in Transepithelial electrical resistance (TEER) (time frame: every 30 min over 2 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02461797, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2015.