Condition category
Genetic Diseases
Date applied
01/12/2015
Date assigned
30/12/2015
Last edited
29/12/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Primary ciliary dyskinesia (PCD) is a rare, inherited condition where there is a problem with the structure or function of the tiny hair-like structures (cilia) in the airways. In an unaffected person, the cilia work as a filter, preventing harmful substances and bacteria from entering the lungs. In a person suffering from PCD, the cilia do not work as they should do which makes the sufferer vulnerable to lung infections and breathing problems. It can be difficult to diagnose PCD, as there is currently no wholly reliable screening technique. Recent studies have shown that measuring nasal nitric oxide (the amount of the gas nitrogen oxide that is breathed out of the nose) may be a good way of screening for PCD, as it has been found that levels are much lower in sufferers than in the general population. The aim of this study is to find out whether using a device to measure nasal nitric oxide (nNO) called the NIOX VERO is able to show the difference in exhaled nitric oxide measurements in PCD sufferers and healthy patients of the same age.

Who can participate?
Patients above 5 years old with confirmed PCD and healthy patients of the same age.

What does the study involve?
All participants attend a single visit at the study centre, which is expected to last between one and two hours. Firstly, a brief medical history is taken, in which the participants are asked about their age, gender, height, weight, race, current medications and living environment. If the participant is a PCD sufferer, then they are also asked about their disease history. After a brief nasal exam (looking into each nostril to make sure they are clear), participants are taught how to use the NIOX VERO (device to measure nasal nitric oxide) with the nasal adapter by the study staff and are given a chance to practice. The participants are then asked to blow their noses and perform a total of two measurements while breathing normally and two measurements while breathing forcefully.

What are the possible benefits and risks of participating?
There are no direct benefits or risks to participants taking part in the study.

Where is the study run from?
University Hospital Southampton NHS Trust (UK) and clinics in Denmark, Germany, France, USA, Ireland and Italy.

When is the study starting and how long is it expected to run for?
January 2016 to May 2016

Who is funding the study?
Aerocrine AB (Sweden)

Who is the main contact?
1. Mrs Margot Berko (Public)
2. Dr Kathy Rickard (Scientific)

Trial website

Contact information

Type

Public

Primary contact

Mrs Margot Berko

ORCID ID

Contact details

Aerocrine Inc.
5151 McCrimmon Parkway
Suite 260
Morrisville
NC
27560
United States of America

Type

Scientific

Additional contact

Dr Kathy Rickard

ORCID ID

Contact details

Aerocrine Inc.
5151 McCrimmon Parkway
Suite 260
Morrisville
NC
27560
United States of America

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

AER-051

Study information

Scientific title

A clinical investigation determining the discriminative ability of the NIOX VERO NASAL to differentiate subjects with primary ciliary dyskinesia from healthy controls

Acronym

Study hypothesis

To determine the feasibility and capability of the NIOX VERO to discriminate subjects with primary ciliary dyskinesia (PCD) from healthy subjects.

Ethics approval

Not provided at time of registration

Study design

Multi-centre cross-sectional study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Other

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Primary ciliary dyskinesia (PCD)

Intervention

There will be one study visit which will last one or two hours.
Participants will be asked basic background questions such as age, sex, height, weight, ethnicity (a group of people who with similar racial origins or cultural background), primary language, environmental tobacco smoke exposure and prior experience with nNO measurements, as well as a brief medical history and review any current medication or other co-existing medical conditions. If participants have PCD, information about specific diagnosis, method of diagnosis and documented allergic history (e.g. asthma, eczema, allergy skin testing, drug allergies etc.) will also be recorded. Participants will also have a brief nasal exam (a simple external look with an otoscope to make sure you can breathe through each nostril and have no nose bleed).
Participants will then be trained by the study staff how to use the NIOX VERO with the nasal adapter and given a chance to practice using the device. They are then asked to blow their nose to clear the nasal passages before performing the measurements. nNO measurements will be performed using two types of breathing methods (Tidal Breathing and Velum Closed ER Method) to attempt to obtain a total a 4 nasal NO measurements. When finished, they will be asked about any discomfort or adverse events.

Intervention type

Other

Phase

Drug names

Primary outcome measures

The concentration of nasal nitric oxide will be measured using the nasal adapter kit for the NIOX VERO during the study visit.

Secondary outcome measures

1. The observed nasal nitric oxide results (ppb)
2. The proportion of participants able to successfully complete nNO measurements using the TB-nNO method
3. The proportion of participants able to successfully complete nNO measurements using the velum closed ER-nNO method
4. The proportion of participants able to successfully complete nNO measurements using both methods

Overall trial start date

06/01/2016

Overall trial end date

13/05/2016

Reason abandoned

Eligibility

Participant inclusion criteria

All participants:
1. Aged 5 years or over
2. Anatomically, is able to complete the nasal NO measurements in both nostrils

PCD patients:
1. Confirmed diagnosis of PCD from one of the PCD diagnostic centres based on clinical phenotype PLUS diagnosis made by at least 1 of the following (the specifics about how diagnosis was made must be documented in their medical file):
1.1. A nasal biopsy or scraping showing a hallmark PCD defect such as, an outer (+/- inner) dynein arm defect, microtubule defect
1.2. A genetic test positive for bi-alleilic mutations in a known PCD-causing gene associated with the diagnosis of PCD (e.g., ARMC4, C21orf59, CCDC39, CCDC40, CCDC65, CCDC164, CCDC103, CCDC114, CCDC151, CCNO, DNAAF1(LRRC50), DNAAF2 (KTU), DNAAF3, DNAH5, DNAH11, DNAI1, DNAI2, DNAL1, DYX1C1, HEATR2, HYDIN, LRRC6, MCIDAS, NME8 (TXNDC3), ODA/IDA, OFD1, RPGR, RSPH3, RSPH4A, RSPH9, SPAG1, ZMYND10)
1.3. A low nasal NO (determined by a chemiluminescent analyser) with either at least 2 separate occasions with ‘hallmark’ changes on high-speed video microscopy, or demonstration of mislocalisation of ciliary proteins by immunofluorescence microscopy (EU Centres Only)

Healthy patients:
1. No airway or immune problems
2. No recent significant injury
3. No systemic infection
4. No systemic inflammation
5. No allergies or asthma

Participant type

Mixed

Age group

Mixed

Gender

Both

Target number of participants

150

Participant exclusion criteria

All participants:
1. Currently smokes or it has been less than 6 months from quitting
2. Has had a nose bleed within the past 2 weeks
3. Has acute respiratory symptoms or signs of an upper or lower respiratory tract infection
4. Use of nasal medication as described below:
4.1. Xolair ≤180 days prior to nNO measurement
4.2. Oral or Systemic Corticosteroids ≤30 days prior to nNO measurement
4.3. Inhaled, nebulized, or intranasal corticosteroids ≤30 days prior to nNO measurement
4.4. Nasal or oral decongestants or antihistamines ≤14 days prior to nNO measurement
4.5. Leukotriene receptor antagonists ≤30 days prior to nNO measurement
5. Has an obstruction or anatomy that prevents a nasal measurement from being performed (as confirmed by simple visual inspection by the Investigator)
6. Has Cystic Fibrosis
7. Has a documented primary or acquired immunodeficiency
8. Is undergoing treatment with NO-releasing drugs (such as nitrates or molsidomine)
9. Has had food or beverage intake (other than water) or has participated in strenuous exercise within 1 hour of nasal NO measurement
10. Is unwilling or unable to provide consent to participate (self, parent or legal guardian)

PCD Patients:
1. Has mutations with RSPH1 since nasal NO may not be low in these patients
2. Has not had a standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease

Healthy Patients:
Atopy or the presence of any of the following: a recent significant injury (i.e., within 1-2 weeks), systemic inflammation, airway or immune problem, asthma or allergies.

Recruitment start date

18/01/2016

Recruitment end date

06/04/2016

Locations

Countries of recruitment

Denmark, France, Germany, Ireland, Italy, United Kingdom, United States of America

Trial participating centre

Hôpital Armand Trousseau
26 Avenue du Dr Arnold Netter
Paris
75571
France

Trial participating centre

University of North Carolina School of Medicine
321 S Columbia Street
Chapel Hill, NC
27599
United States of America

Trial participating centre

University Hospital Southampton NHS Trust
Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Federico II University
Corso Umberto I, 40
Napoli
5-80131
Italy

Trial participating centre

Belfast HSC Trust
Belfast City Hospital Lisburn Road
Belfast
BT12 6BE
Ireland

Trial participating centre

University Children's Hospital Münster
Schlossplatz 2
Münster
48149
Germany

Trial participating centre

Dansk BørneLunge Center
Blegda​msvej 9 2100 København ​Ø
Copenhagen
DK-2100
Denmark

Sponsor information

Organisation

Aerocrine AB

Sponsor details

Råsundavägen 18
8th floor
Solna
SE-171 21
Sweden
+46 8 629 07 80
info@aerocrine.com

Sponsor type

Industry

Website

http://www.aerocrine.com/en/

Funders

Funder type

Industry

Funder name

Aerocrine AB

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date.

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes