Chronic Rhinosinusitis (Diagnosis)NCT03963648
NO Measurements in Screening for Asthma and OSA, in Patients With CRSwNP
A study testing Fractioned Exhaled Nitrogen Oxide measurements in people with Chronic Rhinosinusitis (Diagnosis) and Nasal Polyps, run by Christian von Buchwald at 1 site in Denmark.
Trial summary
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a condition resulting in varying degrees of nasal congestion, nasal secretion, facial pain and reduced or absent sense of smell. In Denmark an estimated 200.000 patients suffer from this condition. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic Rhinosinusitis (Diagnosis), Nasal Polyps, Asthma
- What is being tested?
- Fractioned Exhaled Nitrogen Oxide measurements
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 13 Sep 2019to 1 Jun 2022
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with CRSwNP based on the EPOS2012 criteria
- Polyps in both sides of the nose verified by fiberoptic examination of the nasal cavities
Who cannot join
- Treatment with systemic steroids in the course of the last three months
- Treatment with topical steroids in the course of the last two weeks
- Other inflammatory diseases of the upper airways (i.e. cystic fibrosis, primary ciliary dyskinesis) or immune deficiencies, sarcoidosis or systemic vasculitis
- Infections in the upper airway during the past two weeks
- Smokers
- Treatment with antidepressant or sedative drugs
Show all 9Show fewer
- Age below 18
- Patients unable to give an informed consent
- Patients that do not speak or read Danish
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
University Hospital of Copenhagen, Rigshospitalet
Copenhagen, Capital Region, 2100
Eva Kiær, MD, 26701710, eva.kirkegaard.kiaer.01@regionh.dk
About this study
Official title: Improving Diagnostics of Concurrent Inflammatory Airway Diseases in Private ENT Practice - a Study of NO Measurements in Screening for Asthma and OSA in Patients With CRSwNP
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a condition resulting in varying degrees of nasal congestion, nasal secretion, facial pain and reduced or absent sense of smell. In Denmark an estimated 200.000 patients suffer from this condition. It affects the quality of life in a degree equivalent to chronic cardiac and respiratory conditions.
CRSwNP is known to be associated with inflammation in the nose and sinuses. In some patients the inflammation is also present in the lower airway resulting in shortness of breath, chest constriction, wheezing and coughing. It follows that asthma is often seen in patients with CRSwNP.
Read more
Even though the association of asthma and CRSwNP is well known it is easy to overlook the asthma further reducing the quality of life. Previous studies have found that undiagnosed asthma is present in about a quarter of patients with CRSwNP. While many of the CRSwNP patients are treated in private ENT practice alone the lack of simple diagnostic tests giving a reliable measurement of airway inflammation is a challenge in diagnosing concurrent asthma.
A recent study showed measuring of fractional exhaled nitrogen oxide (FeNO) in exhaled air to be a promising diagnostic test. The concentration of this gas in the exhaled air from the nose and mouth is related to the degree of airway inflammation and can therefore be used as a surrogate measurement in a safe and easy way.
With this study the investigators want to measure the concentration of FeNO in patients with CRSwNP in private ENT practices. The aim is to explore if it can be used as a screening test for asthma. The study will also screen the patients for obstructive sleep apnea (OSA).
Patients will be recruited from three private ENT practices in the Capital Region of Denmark.
Patients with CRSwNP will be recruited from their appointments in the ENT clinics. They will be offered inclusion in the study, and if they give an informed consent, an exhaled NO test and a thorough ENT examination including a fiberoptic examination of the upper airway will be performed. They will also be asked to fill out questionnaires on the severity of symptoms from the nose and lungs, sleep quality and their health in general. Patients will also undergo a sleep study (Cardio-Respiratory Monitoring = CRM) and tests of lung function. With signs of respiratory or sinus disease they will be referred for further investigations and treatment.
Read the detailed description
Hypothesis Exhaled nitrogen oxide (FeNO) is elevated in patients with chronic rhinosinusitis and nasal polyps (CRSwNP). FeNO can be used as screening for concurrent asthma and obstructive sleep apnea (OSA).
Design The study is a prospective, observational multicenter trial. Patients are recruited from three different private specialist ENT-clinics where they will be offered inclusion according to guidelines. They will not be randomized and there will not be a group of patient controls.
The patients will undergo a full ENT-examination including a fiberoptic examination of both nasal cavities and the upper airway. NO-measurements as well as tests of lung function and sleep studies (Cardio-Respiratory-Monitoring = CRM) will also be performed. Furthermore, patients will be asked to fill out three questionnaires (see below). Patients with severe snoring and mild OSA will be offered an evaluation and a DISE (Drug Induced Sedation Endoscopy) at the ENT department Rigshospitalet, Gentofte.
NO-measurements:
FeNO-measurements will be carried out using a handheld NO-device (NIOX VERO, Aerocrine AB, Solna, Sweden). The patients will be asked to blow into a mouthpiece on the device which will then calculate the level of FeNO.
Lung function:
Tests of lung function will be carried out using EasyOne Pulmonary Function Device where the patients will blow into a mouthpiece.
Sleep studies:
Sleep studies (Cardio-Respiratory Monitoring = CRM) will be done as overnight home-studies using SOMNOtouch RESP that will measure heartrate, oxygen saturation, movement of chest and abdomen. All measurements are non-invasive.
Questionnaires:
Patients will be asked to fill out questionnaires regarding nasal symptoms (Sino-Nasal Outcome Test = SNOT-22) along with questionnaires on sleep quality (Epworth Sleepiness Scale = ESS), lung function (ACQ) and general health (The Danish version of Short Form (SF-36) Health Survey) developed at RAND as part of the Medical Outcomes Study (MOS). Danish validated version by Bjørner JB et al.
Statistics Data will be processed using IBM SPSS (Chicago, USA). For categorical data Pearson's Chi2-test or Fischer's exact tests will be used. Students T-test for normally distributed data, while data that are not normally distributed will be analyzed using Mann Whitney U-test. Shapiro-Wilks test or graphic plots will be used in the evaluation of data distribution.
Calculation of Power:
FeNO levels in CRSwNP-patients compared to FeNO levels in CRSwNP-patients with concurrent asthma or OSA.
Expected incidence of a patient with CRSwNP also having asthma: 25% Expected incidence of asthma in the general population: 3% Power: 0.8 Significance: 0.5 Sample size: 10 patients with CRSwNP
Risks, disadvantages and advantages:
There are no known risks associated with the tests of lung function or FeNO measurements. A bit of discomfort with blowing forcefully into the mouthpieces during the tests might occur. The fiberoptic examination of the upper airway might also result in a bit of discomfort. It is expected that paracetamol is sufficient treatment. In the unlikely case that paracetamol is not enough patients will be instructed to contact their physician.
Inclusion in the study will provide the patients with a very thorough examination illuminating any concurrent diseases that might explain their symptoms and discomfort. If any concurrent disease is found, they will be referred for further specialist treatment.
Safety precautions The patients will all be examined by specialists in ENT, who are used to performing these examinations. All will be thoroughly informed about the tests and the motivation for performing them.
In the unlikely event of pronounced discomfort during a test, it will be stopped.
Biobank No tissue samples will be collected.
Data from patient files The investigators have requested access to the patient files in the local IT-systems in the three private ENT clinics as well as via Sundhedsplatformen and FMK (Fælles Medicin Kort) to verify any medical treatment that might interfere with the study as stated in the inclusion and exclusion criteria.
Prior to inclusion, and consent to participate in the study, data on age, previous illness, current medication, and results from the ear-nose-and throat examination will be requested, in order to verify that the participants are eligible for inclusion. The information will be passed on to the investigators.
After inclusion and consent is given to participate in the study, data on allergies, weight, height, age, gender, concurrent illness, and current medication, will be requested.
Consent to participate in the study allows the investigators, sponsors, representatives of sponsors, as well as the supervisory, direct access to collection of data from patient files, including the electronic files, to get information on health-related issues necessary to conduct the research project, self-monitoring, and quality-monitoring, as obligated.
Handling of personal data:
The rules of Databeskyttelsesordningen / persondataforordning will be followed. Data will be stored in accordance with guidelines and only after approval from the local Data Protection Agency (Datatilsynet).
Responsibility for data:
A: Key investigator Eva Kirkegaard Kiær M.D., ENT-specialist Department of otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet, Copenhagen University Hospital Blegdamsvej 9, 2100 København Ø
+ 45 35 45 66 35 / 26 70 17 10 eva.kirkegaard.kiaer.01@regionh.dk
B: Investigator Christian von Buchwald M.D., D.M.Sci Department of otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet, Copenhagen University Hospital Blegdamsvej 9, 2100 København Ø
+ 45 35 45 20 70 christian.von.buchwald@regionh.dk
C: Investigator Nina Vibeke Backer M.D., D.M.Sci Department of Respiratory Medicine Bispebjerg Hospital Ebba Lunds Vej 48, 2400 København NV + 45 38 63 51 22 backer@dadlnet.dk
D: Investigator Andreas Tomaas Ravn M.D., ENT-specialist Frederiksberg øre-næse-halsklinik Falkoner Allé 15, 1. tv., 2000 Frederiksberg + 45 38 87 84 98 atravn@hotmail.com
E: Investigator Steffen Ørntoft M.D., ENT-specialist Øre Næse Hals Klinikken Gammel Køge Landevej 263 1. th., 2650 Hvidovre
+ 45 36 78 88 03 orntoft@dadlnet.dk
F: Investigator Christian Prætorius and Roland Welinder M.D., ENT-specialists Øre-næse-halsklinikken i Hørsholm Kongevejscentret 6, 1. Sal, 2970 Hørsholm
+ 45 45 86 46 00 chr.praetorius@dadlnet.dk
Key investigator is responsible for the safe storage of data in accordance with the guidelines from the local Data Protection Agency (Datatilsynet). Patient data will be stored in a locked cabinet in a locked office.
In accordance with the Danish Law on Health §46, 1+3, the same group of physicians will collect data, process data and publish data. Only investigators A, B and C will process data.
Initiative The initiative for the study is a collaboration between investigator A, B, C and D. All the aforementioned investigators have contributed to the outlines of the study.
Funding The study is partially funded by Fonden for Faglig Udvikling i Speciallægepraksis (FAPS) and Øre-næse-halskirurgisk og Audiologisk Klinik, Rigshospitalet.
All the funding is managed by a research account at Rigshospitalet. The key investigator is employed by the Øre-næse-halskirurgisk and Audiologisk Klinik, Rigshospitalet, but does not have a financial association to FAPS.
Remuneration The patients will not be offered remuneration.
Recruitment Patients will be recruited from three private ENT clinics (investigators D-F). Patients will make appointments for consultation in the clinics as usual, based on their symptoms, and will be offered inclusion in the study if they fall under the inclusion criteria and not the exclusion criteria. All will have the opportunity to consider inclusion in the study and will be offered a new consultation if needed.
Information In accordance with guidelines from the Ethics Committee, participating patients will be given both written and oral information about the study, purpose, and consequences. Patients will receive the folder "Forsøgspersoners rettigheder i et sundhedsvidenskabeligt Forskningsprojekt" published by National Videnskabsetisk Komité (the Central Ethics Committee).
When considering inclusion in the study patients will be offered a new consultation where they can bring an assessor. There will be time and opportunity for any questions they might have. It will take place in an undisturbed location as to ensure a comfortable environment for conversation. Patients will be informed that participation is optional, and their treatment will not be affected should they choose not to accept inclusion.
Patients will be informed of their right to decline information on essential health related issues. The informing physician is responsible for ensuring that the information is understood. The patient has the right to a minimum of one week to consider inclusion.
Informed consent On the day of inclusion, or no later than 14 days after, a written consent will be obtained. The investigator signs the informed consent stating that the patient has received both written and oral information about the project.
Patients will be informed that they can withdraw their informed consent at any given time, and that it will not affect any current or future treatment or consultation.
Should any essential information about a patient's health appear during the study they will be informed accordingly, unless they have clearly stated that they decline such information.
Publication When the results of the study are available, one of the physicians (A-F) will, as far as possible, inform the patients in the study. Information regarding patients is protected by "Lov om behandling af personoplysninger" and "Lov om patienters retstilling (sundhedsloven afsnit III)".
Results, both positive, negative or inconclusive, will be published after the completion of the study. If publication in a peer review journal is not possible, results will be published through other media channels. The study will be registered at www.clinicaltrials.gov
Ethical considerations The study is approved by the local Ethics Committee as well as the Data Protection Agency The purpose of the study is to improve treatment of patients with CRSwNP by diagnosing other conditions that might affect their treatment and quality of life if undiagnosed. The conditions of interest (OSA and asthma) have symptoms that mimic CRSwNP and can therefore be difficult to diagnose if one is not careful to look for them. With this study the investigators hope to find a simple test, associated with minimal discomfort, that might help screen these patients for OSA and asthma.
OSA and asthma are conditions associated with severe consequences on both quality of life and comorbidity. Hopefully a quick diagnosis will help the patients to relevant treatment thus reducing their risk of long-term sequelae.
Any discomfort during the study seems minimal in contrast to the health benefits it will grant patients that are diagnosed with comorbidity as OSA and asthma.
Insurance Patients are covered by "patienterstatningen" during the study period.
- Conditions
- Chronic Rhinosinusitis (Diagnosis), Nasal Polyps, Asthma, Obstructive Sleep Apnea, Airway Disease, Inflammatory Disease
- Being tested
- Fractioned Exhaled Nitrogen Oxide measurements
- Medical subject headings
- Disease, Nasal Polyps, Asthma, Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fractioned Exhaled Nitrogen Oxide measurementsDiagnostic test
Measurements of Fractioned Exhaled Nitrogen Oxide obtained by blowing into a mouthpiece. The NIOX VERO machine will be used for these measures.
| Study group | Role | What they receive |
|---|---|---|
| CRSwNP | Experimental | Study group that will undergo fractioned exhaled nitrogen oxide measurements as well as tests of lungfunction and sleep studies. All tests are non-invasive. Receives: Diagnostic Test: Fractioned Exhaled Nitrogen Oxide measurements |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractioned Exhaled Nitric Oxide levels (FeNO)
Fractioned exhaled nitric oxide (FeNO) parts per billion (ppb) will be measured at an exhalation flow rate of 0.05 L/s, during single exhalation, using a portable nitric oxide analyzer device (NIOX VERO, Circassia AB, P.O. Box 3006 SE-750 03 Uppsala, Sweden).
The normal exhaled NO values during measurements will be set to 5-35 ppb for healthy adults. Patients must produce a 10-second exhalation of breath at an exhalation pressure of 10-20 cmH2O to maintain a stable flow rate of 50±5 mL/s. A calibrated electrochemical sensor evaluates the final 3 seconds of exhalation expressing results in ppb with a range between 5 ppb and 300 ppb. The higher the measurement the larger is the risk of airway inflammation.
Measured: 3 years
Secondary outcomes (7)
Nasal Nitric Oxide levels (nNO)
Nasal Nitric Oxide (nNO) parts per billion (ppb) will be measured both as tidal breathing (TB-nNO) and as expiration against resistance (ER-nNO). A portable nitric oxide analyzer device (NIOX VERO, Circassia AB, Uppsala, Sweden) will be used for all nNO´s.
TB-nNO is a measurement of the level of nitric oxide from one side of the nose as the patient breathes through the open mouth. The device will collect data for 30 s. Results vary in ppb from 5-1500 (580 is the mean for healthy subjects).
ER-nNO will be performed while the patient breathes through the mouth against a restrictor (mouthpiece). After a complete inhalation to the full capacity of the lungs the patient will exhale against the restrictor with the lips closed around the mouthpiece. The patient should exhale steadily for 30 s as the device measures nitric oxide from one side of the nose. Results vary in ppb from 5-1500 with (915 is the mean for healthy subjects).
Measured: 3 years
Apnea Hypopnea Index (AHI)
Cardio Respiratory Monitoring (CRM) will be performed using SOMNOtouch RESP. As an overnight home-study the equipment will measure flow of air and snoring using a nasal cannula. Puls rate, oxygen saturation and heartrate will be measured as well as movement of the thorax and abdomen and body position.
Based on these registrations the system will calculate an AHI (apnea-hypopnea index). This index is the average sum of apneas and hypopneas per hour of sleep. An apnea is a full cessation of breathing for a minimum of 10 s followed by a desaturation of at least 3%. A hypopnea is a 50% or larger reduction in breathing for a minimum of 10s. An index below 5 is normal. An index above 5 is diagnostic of obstructive sleep apnea.
Measured: 3 years
Forced Expiratory Volume in 1 second (FEV1)
Spirometry will be performed using MiniSpir Spiro (Alere A/S Denmark). With a nose clip on the nose patients will be instructed to exhale into a mouthpiece after inhalation to full capacity of the lungs.
The FEV1 (forced expiratory volume in 1 s) is the volume exhaled during the 1st second of a forced exhalation measured in liters. Values below 80 % of the expected normal value, matched by age and height, is considered significantly reduced. The normal value for a 175 cm tall and 50-year-old male is 3,50 L. The normal value for a similar female is 2,99 L.
The FVC (forced vital capacity) is the complete exhaled volume from maximal inhalation to a fast and complete maximal exhalation measured in liters. Values below 80% of the expected normal value, matched by age and height, is considered significantly reduced.
Measured: 3 years
Sino Nasal Outcome Test (questionnaire)
SNOT-22 (Sino Nasal Outcome Test). 22 questions on sino-nasal symptoms. Answers rank from 0-5 where 0 is "not a problem" and 5 is "worst possible problem". Total scores range from 0-110.
Measured: 3 years
Epworth Sleepiness Scale (questionnaire)
ESS (Epworth Sleepiness Scale). 8 questions on daytime sleepiness in every-day situations. Answers rank from 0-3 where 0 is "not a problem" and 3 is "would fall asleep". Total scores range from 0-24. A score higher than 9 is considered excessive daytime sleepiness and indicates a risk of having obstructive sleep apnea.
Measured: 3 years
Short-Form 36 questionnaire
The SF-36 questionnaire (Short Form 36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. The original SF-36 stemmed from the Medical Outcome Study, MOS, which was conducted by the RAND Corporation.
The questionnaire of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The scores are calculated using special software.
Measured: 3 years
ACQ (questionnaire)
ACQ (asthma control questionnaire). The ACQ has 7 questions. Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom and bronchodilator use questions on a 7-point scale (0=no impairment, 6= maximum impairment). Clinic staff score the FEV1% predicted on a 7-point scale. The questions are equally weighted and the ACQ score is the mean of the 7 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).
The ACQ can identify the adequacy of asthma control in individual patients. In general, patients with a score below 1.0 will have adequately controlled asthma and above 1.0 their asthma will not be well controlled.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2019
- Study start13 Sep 2019
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Rhinosinusitis (Diagnosis)Studies of the same condition, open and under way.
- 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christian von Buchwald
- Sponsor type
- University, hospital or other
- Collaborators
- Bispebjerg Hospital
- Responsible party
- Sponsor-investigator, Christian von Buchwald, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Eva K Kiær, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03963648
- Sponsor's protocol ID
- CRS07052019NOEKK
- Status last verified
- Sep 2021
- First submitted
- 8 May 2019
- Last updated
- 16 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Diagnostics of Concurrent Inflammatory Airway Diseases in Private ENT Practice - a Study of NO Measurements in Screening for Asthma and OSA in Patients With CRSwNP
- ClinicalTrials.gov ID
- NCT03963648
- Acronym / sponsor ID
- CRS07052019NOEKK
- Conditions
- Chronic Rhinosinusitis (Diagnosis), Nasal Polyps, Asthma, Obstructive Sleep Apnea, Airway Disease, Inflammatory Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Christian von BuchwaldUniversity, hospital or other
- Collaborators
- Bispebjerg Hospital
- Study start
- 13 Sep 2019 (actual)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Jun 2022 (estimated)
- First posted
- 28 May 2019 (actual)
- 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.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a condition resulting in varying degrees of nasal congestion, nasal secretion, facial pain and reduced or absent sense of smell. In Denmark an estimated 200.000 patients suffer from this condition. It affects the quality of life in a degree equivalent to chronic cardiac and respiratory conditions.
CRSwNP is known to be associated with inflammation in the nose and sinuses. In some patients the inflammation is also present in the lower airway resulting in shortness of breath, chest constriction, wheezing and coughing. It follows that asthma is often seen in patients with CRSwNP.
Even though the association of asthma and CRSwNP is well known it is easy to overlook the asthma further reducing the quality of life. Previous studies have found that undiagnosed asthma is present in about a quarter of patients with CRSwNP. While many of the CRSwNP patients are treated in private ENT practice alone the lack of simple diagnostic tests giving a reliable measurement of airway inflammation is a challenge in diagnosing concurrent asthma.
A recent study showed measuring of fractional exhaled nitrogen oxide (FeNO) in exhaled air to be a promising diagnostic test. The concentration of this gas in the exhaled air from the nose and mouth is related to the degree of airway inflammation and can therefore be used as a surrogate measurement in a safe and easy way.
With this study the investigators want to measure the concentration of FeNO in patients with CRSwNP in private ENT practices. The aim is to explore if it can be used as a screening test for asthma. The study will also screen the patients for obstructive sleep apnea (OSA).
Patients will be recruited from three private ENT practices in the Capital Region of Denmark.
Patients with CRSwNP will be recruited from their appointments in the ENT clinics. They will be offered inclusion in the study, and if they give an informed consent, an exhaled NO test and a thorough ENT examination including a fiberoptic examination of the upper airway will be performed. They will also be asked to fill out questionnaires on the severity of symptoms from the nose and lungs, sleep quality and their health in general. Patients will also undergo a sleep study (Cardio-Respiratory Monitoring = CRM) and tests of lung function. With signs of respiratory or sinus disease they will be referred for further investigations and treatment.
Detailed description
Hypothesis Exhaled nitrogen oxide (FeNO) is elevated in patients with chronic rhinosinusitis and nasal polyps (CRSwNP). FeNO can be used as screening for concurrent asthma and obstructive sleep apnea (OSA).
Design The study is a prospective, observational multicenter trial. Patients are recruited from three different private specialist ENT-clinics where they will be offered inclusion according to guidelines. They will not be randomized and there will not be a group of patient controls.
The patients will undergo a full ENT-examination including a fiberoptic examination of both nasal cavities and the upper airway. NO-measurements as well as tests of lung function and sleep studies (Cardio-Respiratory-Monitoring = CRM) will also be performed. Furthermore, patients will be asked to fill out three questionnaires (see below). Patients with severe snoring and mild OSA will be offered an evaluation and a DISE (Drug Induced Sedation Endoscopy) at the ENT department Rigshospitalet, Gentofte.
NO-measurements:
FeNO-measurements will be carried out using a handheld NO-device (NIOX VERO, Aerocrine AB, Solna, Sweden). The patients will be asked to blow into a mouthpiece on the device which will then calculate the level of FeNO.
Lung function:
Tests of lung function will be carried out using EasyOne Pulmonary Function Device where the patients will blow into a mouthpiece.
Sleep studies:
Sleep studies (Cardio-Respiratory Monitoring = CRM) will be done as overnight home-studies using SOMNOtouch RESP that will measure heartrate, oxygen saturation, movement of chest and abdomen. All measurements are non-invasive.
Questionnaires:
Patients will be asked to fill out questionnaires regarding nasal symptoms (Sino-Nasal Outcome Test = SNOT-22) along with questionnaires on sleep quality (Epworth Sleepiness Scale = ESS), lung function (ACQ) and general health (The Danish version of Short Form (SF-36) Health Survey) developed at RAND as part of the Medical Outcomes Study (MOS). Danish validated version by Bjørner JB et al.
Statistics Data will be processed using IBM SPSS (Chicago, USA). For categorical data Pearson's Chi2-test or Fischer's exact tests will be used. Students T-test for normally distributed data, while data that are not normally distributed will be analyzed using Mann Whitney U-test. Shapiro-Wilks test or graphic plots will be used in the evaluation of data distribution.
Calculation of Power:
FeNO levels in CRSwNP-patients compared to FeNO levels in CRSwNP-patients with concurrent asthma or OSA.
Expected incidence of a patient with CRSwNP also having asthma: 25% Expected incidence of asthma in the general population: 3% Power: 0.8 Significance: 0.5 Sample size: 10 patients with CRSwNP
Risks, disadvantages and advantages:
There are no known risks associated with the tests of lung function or FeNO measurements. A bit of discomfort with blowing forcefully into the mouthpieces during the tests might occur. The fiberoptic examination of the upper airway might also result in a bit of discomfort. It is expected that paracetamol is sufficient treatment. In the unlikely case that paracetamol is not enough patients will be instructed to contact their physician.
Inclusion in the study will provide the patients with a very thorough examination illuminating any concurrent diseases that might explain their symptoms and discomfort. If any concurrent disease is found, they will be referred for further specialist treatment.
Safety precautions The patients will all be examined by specialists in ENT, who are used to performing these examinations. All will be thoroughly informed about the tests and the motivation for performing them.
In the unlikely event of pronounced discomfort during a test, it will be stopped.
Biobank No tissue samples will be collected.
Data from patient files The investigators have requested access to the patient files in the local IT-systems in the three private ENT clinics as well as via Sundhedsplatformen and FMK (Fælles Medicin Kort) to verify any medical treatment that might interfere with the study as stated in the inclusion and exclusion criteria.
Prior to inclusion, and consent to participate in the study, data on age, previous illness, current medication, and results from the ear-nose-and throat examination will be requested, in order to verify that the participants are eligible for inclusion. The information will be passed on to the investigators.
After inclusion and consent is given to participate in the study, data on allergies, weight, height, age, gender, concurrent illness, and current medication, will be requested.
Consent to participate in the study allows the investigators, sponsors, representatives of sponsors, as well as the supervisory, direct access to collection of data from patient files, including the electronic files, to get information on health-related issues necessary to conduct the research project, self-monitoring, and quality-monitoring, as obligated.
Handling of personal data:
The rules of Databeskyttelsesordningen / persondataforordning will be followed. Data will be stored in accordance with guidelines and only after approval from the local Data Protection Agency (Datatilsynet).
Responsibility for data:
A: Key investigator Eva Kirkegaard Kiær M.D., ENT-specialist Department of otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet, Copenhagen University Hospital Blegdamsvej 9, 2100 København Ø
+ 45 35 45 66 35 / 26 70 17 10 eva.kirkegaard.kiaer.01@regionh.dk
B: Investigator Christian von Buchwald M.D., D.M.Sci Department of otorhinolaryngology, Head and Neck Surgery and Audiology Rigshospitalet, Copenhagen University Hospital Blegdamsvej 9, 2100 København Ø
+ 45 35 45 20 70 christian.von.buchwald@regionh.dk
C: Investigator Nina Vibeke Backer M.D., D.M.Sci Department of Respiratory Medicine Bispebjerg Hospital Ebba Lunds Vej 48, 2400 København NV + 45 38 63 51 22 backer@dadlnet.dk
D: Investigator Andreas Tomaas Ravn M.D., ENT-specialist Frederiksberg øre-næse-halsklinik Falkoner Allé 15, 1. tv., 2000 Frederiksberg + 45 38 87 84 98 atravn@hotmail.com
E: Investigator Steffen Ørntoft M.D., ENT-specialist Øre Næse Hals Klinikken Gammel Køge Landevej 263 1. th., 2650 Hvidovre
+ 45 36 78 88 03 orntoft@dadlnet.dk
F: Investigator Christian Prætorius and Roland Welinder M.D., ENT-specialists Øre-næse-halsklinikken i Hørsholm Kongevejscentret 6, 1. Sal, 2970 Hørsholm
+ 45 45 86 46 00 chr.praetorius@dadlnet.dk
Key investigator is responsible for the safe storage of data in accordance with the guidelines from the local Data Protection Agency (Datatilsynet). Patient data will be stored in a locked cabinet in a locked office.
In accordance with the Danish Law on Health §46, 1+3, the same group of physicians will collect data, process data and publish data. Only investigators A, B and C will process data.
Initiative The initiative for the study is a collaboration between investigator A, B, C and D. All the aforementioned investigators have contributed to the outlines of the study.
Funding The study is partially funded by Fonden for Faglig Udvikling i Speciallægepraksis (FAPS) and Øre-næse-halskirurgisk og Audiologisk Klinik, Rigshospitalet.
All the funding is managed by a research account at Rigshospitalet. The key investigator is employed by the Øre-næse-halskirurgisk and Audiologisk Klinik, Rigshospitalet, but does not have a financial association to FAPS.
Remuneration The patients will not be offered remuneration.
Recruitment Patients will be recruited from three private ENT clinics (investigators D-F). Patients will make appointments for consultation in the clinics as usual, based on their symptoms, and will be offered inclusion in the study if they fall under the inclusion criteria and not the exclusion criteria. All will have the opportunity to consider inclusion in the study and will be offered a new consultation if needed.
Information In accordance with guidelines from the Ethics Committee, participating patients will be given both written and oral information about the study, purpose, and consequences. Patients will receive the folder "Forsøgspersoners rettigheder i et sundhedsvidenskabeligt Forskningsprojekt" published by National Videnskabsetisk Komité (the Central Ethics Committee).
When considering inclusion in the study patients will be offered a new consultation where they can bring an assessor. There will be time and opportunity for any questions they might have. It will take place in an undisturbed location as to ensure a comfortable environment for conversation. Patients will be informed that participation is optional, and their treatment will not be affected should they choose not to accept inclusion.
Patients will be informed of their right to decline information on essential health related issues. The informing physician is responsible for ensuring that the information is understood. The patient has the right to a minimum of one week to consider inclusion.
Informed consent On the day of inclusion, or no later than 14 days after, a written consent will be obtained. The investigator signs the informed consent stating that the patient has received both written and oral information about the project.
Patients will be informed that they can withdraw their informed consent at any given time, and that it will not affect any current or future treatment or consultation.
Should any essential information about a patient's health appear during the study they will be informed accordingly, unless they have clearly stated that they decline such information.
Publication When the results of the study are available, one of the physicians (A-F) will, as far as possible, inform the patients in the study. Information regarding patients is protected by "Lov om behandling af personoplysninger" and "Lov om patienters retstilling (sundhedsloven afsnit III)".
Results, both positive, negative or inconclusive, will be published after the completion of the study. If publication in a peer review journal is not possible, results will be published through other media channels. The study will be registered at www.clinicaltrials.gov
Ethical considerations The study is approved by the local Ethics Committee as well as the Data Protection Agency The purpose of the study is to improve treatment of patients with CRSwNP by diagnosing other conditions that might affect their treatment and quality of life if undiagnosed. The conditions of interest (OSA and asthma) have symptoms that mimic CRSwNP and can therefore be difficult to diagnose if one is not careful to look for them. With this study the investigators hope to find a simple test, associated with minimal discomfort, that might help screen these patients for OSA and asthma.
OSA and asthma are conditions associated with severe consequences on both quality of life and comorbidity. Hopefully a quick diagnosis will help the patients to relevant treatment thus reducing their risk of long-term sequelae.
Any discomfort during the study seems minimal in contrast to the health benefits it will grant patients that are diagnosed with comorbidity as OSA and asthma.
Insurance Patients are covered by "patienterstatningen" during the study period.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CRSwNP | Experimental | Diagnostic Test: Fractioned Exhaled Nitrogen Oxide measurementsStudy group that will undergo fractioned exhaled nitrogen oxide measurements as well as tests of lungfunction and sleep studies. All tests are non-invasive. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with CRSwNP based on the EPOS2012 criteria
- Polyps in both sides of the nose verified by fiberoptic examination of the nasal cavities
Key exclusion criteria (9 listed)
- Treatment with systemic steroids in the course of the last three months
- Treatment with topical steroids in the course of the last two weeks
- Other inflammatory diseases of the upper airways (i.e. cystic fibrosis, primary ciliary dyskinesis) or immune deficiencies, sarcoidosis or systemic vasculitis
- Infections in the upper airway during the past two weeks
- Smokers
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 |
|---|---|---|
| Fractioned Exhaled Nitrogen Oxide measurementsMeasurements of Fractioned Exhaled Nitrogen Oxide obtained by blowing into a mouthpiece. The NIOX VERO machine will be used for these measures. | Diagnostic test | CRSwNP |
Primary outcome
Fractioned Exhaled Nitric Oxide levels (FeNO)
Time frame: 3 years
Fractioned exhaled nitric oxide (FeNO) parts per billion (ppb) will be measured at an exhalation flow rate of 0.05 L/s, during single exhalation, using a portable nitric oxide analyzer device (NIOX VERO, Circassia AB, P.O. Box 3006 SE-750 03 Uppsala, Sweden). The normal exhaled NO values during measurements will be set to 5-35 ppb for healthy adults. Patients must produce a 10-second exhalation of breath at an exhalation pressure of 10-20 cmH2O to maintain a stable flow rate of 50±5 mL/s. A calibrated electrochemical sensor evaluates the final 3 seconds of exhalation expressing results in ppb with a range between 5 ppb and 300 ppb. The higher the measurement the larger is the risk of airway inflammation.
7 secondary outcomes
Nasal Nitric Oxide levels (nNO)
Time frame: 3 years
Apnea Hypopnea Index (AHI)
Time frame: 3 years
Forced Expiratory Volume in 1 second (FEV1)
Time frame: 3 years
Sino Nasal Outcome Test (questionnaire)
Time frame: 3 years
Epworth Sleepiness Scale (questionnaire)
Time frame: 3 years
Short-Form 36 questionnaire
Time frame: 3 years
ACQ (questionnaire)
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2021.
- Individual participant dataSharing planned: No
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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.
Eva K Kiær principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fractioned Exhaled Nitrogen Oxide measurements in people with Chronic Rhinosinusitis (Diagnosis) and Nasal Polyps, run by Christian von Buchwald at 1 site in Denmark.
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 2 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 16 Sep 2021. 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 Denmark. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eva K Kiaer, M.D. (+45 35 45 66 35, eva.kirkegaard.kiaer.01@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fractioned Exhaled Nitric Oxide levels (FeNO) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2021.