Response of the Airway in Sinusitis and Asthma (RAISe)

August 12, 2019 updated by: Pawel Majak, Medical University of Lodz

The Role of Nonspecific Immune Response of the Airway Mucosa in Children With Chronic Rhinosinusitis and Asthma

The project is intended to be realised in two phases. In the first stage, a case control study will be performed. In the second phase, double-blind, placebo controlled study will be conducted. In the first phase 3 groups of children will be compare: i) a group of children suffering from chronic rhinosinusitis (CRS) (fulfilling the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria) and asthma (fulfilling the Asthma Predictive Index (API) criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of intranasal glucocorticosteroids will be assessed. The following research methods will be used: CRS-symptom score questionnaire (SN-5) and Childhood Asthma Control Test (cACT) questionnaires, skin prick test, spirometry, measurement of nitric oxide NO in exhaled breath (FeNO), taste perception test, eosinophil morphology assessment, ratio: glucose concentration in nasal secretion/serum glucose level, concentration of specific immunoglobulin (Ig) E, total immunoglobulin G (IgG) and immunoglobulin A (IgA), the proportion of innate lymphoid cells (ILC) and regulatory lymphocytes cells in the peripheral blood. Endoscopic examination of the upper airways will be performed and samples of the mucosa will be taken. The mucosal examination will be as follows: i) polymerase chain reaction (PCR) examination for the detection of the presence of viral and bacterial genetic material, ii) measurement of the expression of the various messenger ribonucleic acid (mRNA), iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILCs.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Persistence of CRS and asthma require multiple interconnected feedback and feed-forward circuits between ILCs and epithelial cells. It seems that type 2 ILCs (ILC2) are the most important accelerators of type II immune response that prepare cytokine microenvironment for Th2 cells chronic activation. What decide on ILC2 accumulation - this is an urgent question. The aim of the proposed project is to examine the role of the innate immune response of airways in children suffering from chronic rhinosinusitis and asthma.

The project is intended to be realised in two phases. In the first stage, a case control study will be performed. In the second phase, double-blind, placebo controlled study will be conducted. In the first phase 3 groups of children will be compare: i) a group of children suffering from CRS (fulfilling the EPOS criteria) and asthma (fulfilling the API criteria) (CRS+/asthma+, n=90), ii) a group of children suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria) (CRS+/asthma-, n=30) and iii) a group of children without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria) (CRS-/asthma-, n=30). In the second phase the effect of intranasal glucocorticosteroids will be assessed. The following research methods will be used: SN-5 and cACT questionnaires, skin prick test, spirometry, measurement of NO in exhaled breath, taste perception test, eosinophil morphology assessment, ratio: glucose concentration in nasal secretion/serum glucose level, concentration of specific immunoglobulin E, total IgG and IgA, the proportion of ILC2 cells and regulatory cells in the peripheral blood. Endoscopic examination of the upper airways will be performed and samples of the mucosa will be taken. The mucosal examination will be as follows: i) PCR examination for the detection of the presence of viral and bacterial genetic material, ii) measurement of the expression of the various mRNA types, iii) measurement of the expression of mRNA for the Epithelial-Mesenchymal Transition (EMT) genes and iv) percentage of ILC 1, 2 and 3 cells and regulatory cells.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
      • Lodz, Poland, 90-153
        • Department of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 8 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • a group of children (n=90) suffering from CRS (fulfilling the EPOS criteria, European Position Paper on Rhinosinusitis and Nasal Polyps) and asthma (fulfilling the API criteria, Asthma Predictive Index), including a 30-person subgroup diagnosed with clinically significant IgE-dependent hypersensitivity (accordance between symptoms and current exposure to sensitizing allergen),
  • a group of children (n=30) suffering from CRS (fulfilling the EPOS criteria) but without asthma symptoms (negative API criteria), including a 15-person subgroup diagnosed with clinically significant IgE-dependent hypersensitivity (accordance between symptoms and current exposure to sensitizing allergen),
  • a group of children (n=30) without symptoms of CRS (negative EPOS criteria) and without asthma symptoms (negative API criteria).

Exclusion Criteria:

  • food allergy with symptoms affecting the respiratory tract
  • contraindication to nasal endoscopy or contraindication to nasal mucosa biopsy
  • hypertrophy of the third tonsil exceeding 60% of the nasopharynx (the criterion of obstruction being an indication for adenoidectomy). In these patients, the anatomical nasal obstruction may be the single cause of chronic inflammation in the airways, and hence verification of the hypotheses is impossible
  • confirmed immunodeficiency
  • exacerbation of asthma requiring systemic administration of glucocorticosteroids
  • obesity, exposure to tobacco smoke
  • other chronic illnesses and clinical conditions, which in the opinion of the researcher may influence the evaluation and the course of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: mometasone nasal
a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months,
Drug: Mometasone Nasal
a group of children who will receive a nasal mometasone in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% Sodium chloride (NaCl) solution in a nasal nebuliser once a day for 3 months
Other Names:
  • NasometinTM, Sandoz
PLACEBO_COMPARATOR: placebo mometasone
a group of children without immunoglobulin E (IgE) - dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,
Drug: placebo mometasone
a group of children without IgE-dependent hypersensitivity who will receive nasal mometasone placebo in an atomiser for three months (one application, once per day) and supplemental 3ml 0.9% NaCl solution in a nasal nebuliser once a day for 3 months,
Other Names:
  • placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Asthma Control Test for children (cACT™)
Time Frame: 12 months
Childhood Asthma Control Test (cACT™), will be used, which has been recommended by the Global Initiative for Asthma (GINA) Report
12 months
SN-5
Time Frame: 12 months
validated questionnaire for the assessment for quality of life in children with CRS (5 symptom-cluster items covering the domains of sinus infection, nasal obstruction, allergy symptoms, emotional distress, and activity limitations)
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Spirometry
Time Frame: 12 months
Respiratory function tests will be performed according to the American Thoracic Society (ATS) standards. The best result of three spirometric maneuvers will be selected for the analysis of obstructive disorders and the level of disease severity according to the standards of the Polish Society of Lung Diseases. The analysis will include FEV1% (A/N% - the percent of the measured to predicted value).
12 months
Nasal fraction of exhaled nitric oxide (nFeNO) Measurements
Time Frame: 12 months
Measurements of nasal fraction of exhaled nitric oxide (nFeNO) will be performed using an electrochemical analyzer (ExpAir) according to the manufacturer's instructions. The detection limit ranged from 1 ppb to 6000 ppb.
12 months
Glucose concentration
Time Frame: 12 months
Glucose concentration in serum and in nasal secretions will be assessed using glucose oxidase sticks (Roche, Lewes, East Sussex, U.K.). Nasal glucose concentration will analyzed in the context of blood glucose level using following ratio: nasal glucose level/blood glucose level.
12 months
Immunophenotyping
Time Frame: 12 months
Mucosa - The nasal mucosa sample will be gently processed (mechanical dissociation, mild enzyme digestion) to produce a single cell suspension. It will be further fixed and stained with specific cocktail of fluorescent dye-stained antibody and then cell identification will be performed by flow cytometry. The relative count of all cell subsets will be determined. All procedures will be performed in buffers containing brefeldin and/or monesin to prevent dislocation of proteins of interest.
12 months
quantitative polymerase chain reaction (qPCR)
Time Frame: 12 months

Total RNA will be isolated from mucosa samples and then reverse-transcribed with e.g. Thermo Scientific Maxima Reverse Transcriptase. qPCR reaction will be performed using house-designed primer sets. Relative expression of genes of interest (involved in innate response) will be analyzed against selected house-keeping gene transcripts.

Manufacturer recommended procedure will be used to quantify Human Epithelial to Mesenchymal Transition gene panel and Multiplex Real-Time PCR for pathogen genes
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Lodz

Investigators

  • Principal Investigator: Pawel Majak, MD, PhD, Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital,

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 1, 2017

Primary Completion (ACTUAL)

August 1, 2019

Study Completion (ACTUAL)

August 1, 2019

Study Registration Dates

First Submitted

January 2, 2017

First Submitted That Met QC Criteria

January 3, 2017

First Posted (ESTIMATE)

January 5, 2017

Study Record Updates

Last Update Posted (ACTUAL)

August 13, 2019

Last Update Submitted That Met QC Criteria

August 12, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RNN/153/16/KE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Asthma

Clinical Trials on Mometasone Nasal

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Oman

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe