Ciliary Motility DisordersnNO_PCDNCT04949308
Nasal Nitric Oxide Across Mutations in Primary Ciliary Dyskinesia
An observational study of Ciliary Motility Disorders and Primary Ciliary Dyskinesia, run by University Hospital Muenster at 1 site in Germany.
Trial summary
Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways, laterality defects (Situs inversus totalis in about 50% of cases) and fertility problems. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ciliary Motility Disorders, Primary Ciliary Dyskinesia
- How many people
- 2,000 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jan 2021to 31 Dec 2022
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
Who may be able to join
- Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
- PCD individuals of all age groups with at least one nNO measurement performed according to diagnostic guidelines. Serial nNO measurements should be included if available (e.g. yearly), at least for infants and young children
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Münster
Münster, North Rhine-Westphalia, 48149
Heymut Omran, Prof, Dr, MD, +4925183 ext. 41097, PCDregistry.eu@ukmuenster.de
Simone Helms, +4925183 ext. 48358, Simone.Helms@ukmuenster.de
About this study
Official title: High or Low. Nasal Nitric Oxide Across Mutations in Primary Ciliary Dyskinesia. A Genotype/Phenotype Analysis of Nasal NO in Patients With PCD Within the European Reference Network (ERN)
Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways, laterality defects (Situs inversus totalis in about 50% of cases) and fertility problems. At present, mutations in > 45 genes associated with PCD and mucociliary clearance disorders have been identified, representing most likely two thirds of all human cases.
The aims of this study are:
- Correlation between nasal NO levels and distinct PCD genotypes
- Determination of further parameters potentially associated with nasal NO levels in genotyped PCD individuals
- course of clinical manifestations (e.g. neonatal distress, infections, bronchiectasis)
- diagnostic results (HVMA, TEM, IF)
- lung function outcome (FVC, FEV1)
Read the detailed description
Nasal Nitric Oxide (nNO) concentration is usually low or very low in patients with Primary Ciliary Dyskinesia (PCD) for yet unknown reasons (1).
Measured nNO holds a strong ability to separate healthy subjects from patients with PCD in both childhood and adulthood and across several different nNO sampling modalities (2) (3-5) and nNO is widely used as an important supplementary diagnostic test for PCD work up in both Europe (6) and North America (7). Low nNO in PCD was first reported 26 years ago (8). Nasal NO has been associated with host paranasal sinus defense as sufficient nNO production in non-PCD subjects is thought to play a role in maintaining paranasal sinus sterility (9). Furhermore, ciliary beating seems to be upregulated by a NO dependent pathway in bovine airway epithelium (10), influencing mucociliary clearance. However, human in vitro studies of ciliated airway cells in air-liquid-interface (ALI) culture have been ambiguous as to whether the biosynthesis of NO in PCD is impaired (11) (12) or not (13; 14) and the etiology of low nNO in PCD and presumed link to ciliary beating remains unclear. So far, attempts to link PCD phenotype and genotype has indicated that patients with PCD harboring CCDC39 and CCDC40 mutations may have a poorer lung function development (15).
In rare cases of PCD (<5%) (16) nNO concentration is within normal range. More than 14 different PCD-causing genes (e.g RSPH1, GAS8, RPGR, CCNO, CCDC103, CFAP221, DNAH9, FOXJ1, GAS2L2, LRRC56, NEK10, SPEF2, STK36, TTC12) has been associated with nNO values above the agreed cut off for nNO-production rate of 77 nL/min in a few patients with PCD (16). However, individuals with NEK10 or FOXJ1 mutations, for example, display a very severe respiratory phenotype (17), but making a diagnosis is challenging because of normal nNO values as well as apparently normal ciliary beating.
Since nNO also holds potential as an outcome parameter in future clinical trials of PCD, better understanding of nNO in PCD is warranted.
Demand of large number of patients with PCD is crucial, keeping the rareness of nearnormal and normal nNO levels in PCD in mind. Motivated by the analysis of lung function in a large cohort of genotyped PCD-patients, this multicenter Involvement across international PCD centers is an obvious opportunity for gaining such further knowledge with the focus on nasal NO.
The aims of this study are:
- Correlation between nasal NO levels and distinct PCD genotypes
- Determination of further parameters potentially associated with nasal NO levels in genotyped PCD individuals
- course of clinical manifestations (e.g. neonatal distress, infections, bronchiectasis)
- diagnostic results (HVMA, TEM, IF)
- lung function outcome (FVC, FEV1)
Inclusion criteria:
- Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
- PCD individuals of all age groups with at least one nNO measurement performed according to diagnostic guidelines. Serial nNO measurements should be included if available (e.g. yearly), at least for infants and young children
- Medical subject headings
- Ciliary Motility Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Genetic diagnosis | Genetic: Genetic diagnosis No Intervention foreseen, but genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD and at least one other method confirming PCD-diagnosis is needed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genotype-nasal Nitric Oxide Corelation
nNO in correlation to the genetic make-up
Measured: up to 20 years retrospective
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2021
- Study start1 Jan 2021
- Primary completion30 Jun 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ciliary Motility DisordersStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Hospital Vall d'Hebron, KU Leuven, Amsterdam UMC, location VUmc, University of Valencia, NOVA Medical School, University of Geneva, Switzerland, University of Bern, Ruhr University of Bochum, Charite University, Berlin, Germany, Hannover Medical School, Medical University of Vienna, Royal Brompton & Harefield NHS Foundation Trust, University College, London, University of Dundee, University of Southampton, University of Leicester, University of Pisa, Federico II University, Bambino Gesù Hospital and Research Institute, University of Nicosia, Oslo University Hospital, Hospital de Niños R. Gutierrez de Buenos Aires, Hacettepe University, Marmara University, University Hospital, Motol, University Children's Hospital, Zurich, The Leeds Teaching Hospitals NHS Trust, Hadassah Medical Organization, Göteborg University, Schneider Children's Medical Center, Israel, University of Sao Paulo, University Hospital of Cologne, University of Belgrade, University Hospital, Martin, Abderrahmane Mami Hospital
- Responsible party
- Sponsor
- Investigators
- Heymut Omran, Prof,Dr,MD, Study chair, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04949308
- Sponsor's protocol ID
- JR_nNO_PCD_09_2020
- Acronym
- nNO_PCD
- Status last verified
- Jun 2021
- First submitted
- 24 Jun 2021
- Last updated
- 2 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High or Low. Nasal Nitric Oxide Across Mutations in Primary Ciliary Dyskinesia. A Genotype/Phenotype Analysis of Nasal NO in Patients With PCD Within the European Reference Network (ERN)
- ClinicalTrials.gov ID
- NCT04949308
- Acronym / sponsor ID
- nNO_PCD / JR_nNO_PCD_09_2020
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Hospital Vall d'Hebron, KU Leuven, Amsterdam UMC, location VUmc, University of Valencia, NOVA Medical School, University of Geneva, Switzerland, University of Bern, Ruhr University of Bochum, Charite University, Berlin, Germany, Hannover Medical School, Medical University of Vienna, Royal Brompton & Harefield NHS Foundation Trust, University College, London, University of Dundee, University of Southampton, University of Leicester, University of Pisa, Federico II University, Bambino Gesù Hospital and Research Institute, University of Nicosia, Oslo University Hospital, Hospital de Niños R. Gutierrez de Buenos Aires, Hacettepe University, Marmara University, University Hospital, Motol, University Children's Hospital, Zurich, The Leeds Teaching Hospitals NHS Trust, Hadassah Medical Organization, Göteborg University, Schneider Children's Medical Center, Israel, University of Sao Paulo, University Hospital of Cologne, University of Belgrade, University Hospital, Martin, Abderrahmane Mami Hospital
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 2 Jul 2021 (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.
Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways, laterality defects (Situs inversus totalis in about 50% of cases) and fertility problems. At present, mutations in > 45 genes associated with PCD and mucociliary clearance disorders have been identified, representing most likely two thirds of all human cases.
The aims of this study are:
- Correlation between nasal NO levels and distinct PCD genotypes
- Determination of further parameters potentially associated with nasal NO levels in genotyped PCD individuals
- course of clinical manifestations (e.g. neonatal distress, infections, bronchiectasis)
- diagnostic results (HVMA, TEM, IF)
- lung function outcome (FVC, FEV1)
Detailed description
Nasal Nitric Oxide (nNO) concentration is usually low or very low in patients with Primary Ciliary Dyskinesia (PCD) for yet unknown reasons (1).
Measured nNO holds a strong ability to separate healthy subjects from patients with PCD in both childhood and adulthood and across several different nNO sampling modalities (2) (3-5) and nNO is widely used as an important supplementary diagnostic test for PCD work up in both Europe (6) and North America (7). Low nNO in PCD was first reported 26 years ago (8). Nasal NO has been associated with host paranasal sinus defense as sufficient nNO production in non-PCD subjects is thought to play a role in maintaining paranasal sinus sterility (9). Furhermore, ciliary beating seems to be upregulated by a NO dependent pathway in bovine airway epithelium (10), influencing mucociliary clearance. However, human in vitro studies of ciliated airway cells in air-liquid-interface (ALI) culture have been ambiguous as to whether the biosynthesis of NO in PCD is impaired (11) (12) or not (13; 14) and the etiology of low nNO in PCD and presumed link to ciliary beating remains unclear. So far, attempts to link PCD phenotype and genotype has indicated that patients with PCD harboring CCDC39 and CCDC40 mutations may have a poorer lung function development (15).
In rare cases of PCD (<5%) (16) nNO concentration is within normal range. More than 14 different PCD-causing genes (e.g RSPH1, GAS8, RPGR, CCNO, CCDC103, CFAP221, DNAH9, FOXJ1, GAS2L2, LRRC56, NEK10, SPEF2, STK36, TTC12) has been associated with nNO values above the agreed cut off for nNO-production rate of 77 nL/min in a few patients with PCD (16). However, individuals with NEK10 or FOXJ1 mutations, for example, display a very severe respiratory phenotype (17), but making a diagnosis is challenging because of normal nNO values as well as apparently normal ciliary beating.
Since nNO also holds potential as an outcome parameter in future clinical trials of PCD, better understanding of nNO in PCD is warranted.
Demand of large number of patients with PCD is crucial, keeping the rareness of nearnormal and normal nNO levels in PCD in mind. Motivated by the analysis of lung function in a large cohort of genotyped PCD-patients, this multicenter Involvement across international PCD centers is an obvious opportunity for gaining such further knowledge with the focus on nasal NO.
The aims of this study are:
- Correlation between nasal NO levels and distinct PCD genotypes
- Determination of further parameters potentially associated with nasal NO levels in genotyped PCD individuals
- course of clinical manifestations (e.g. neonatal distress, infections, bronchiectasis)
- diagnostic results (HVMA, TEM, IF)
- lung function outcome (FVC, FEV1)
Inclusion criteria:
- Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
- PCD individuals of all age groups with at least one nNO measurement performed according to diagnostic guidelines. Serial nNO measurements should be included if available (e.g. yearly), at least for infants and young children
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Genetic diagnosis | – | –Genetic: Genetic diagnosis No Intervention foreseen, but genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD and at least one other method confirming PCD-diagnosis is needed |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
Key inclusion criteria (2 listed)
- Patients with a genetically confirmed diagnosis of PCD (bi-allelic mutations in a gene, known to cause PCD) with typical clinical symptoms of PCD
- PCD individuals of all age groups with at least one nNO measurement performed according to diagnostic guidelines. Serial nNO measurements should be included if available (e.g. yearly), at least for infants and young children
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Genotype-nasal Nitric Oxide Corelation
Time frame: up to 20 years retrospective
nNO in correlation to the genetic make-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2021.
- Individual participant dataSharing planned: Undecided
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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.
Heymut Omran, Prof,Dr,MD study chair
University Hospital Muenster
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ciliary Motility Disorders and Primary Ciliary Dyskinesia, run by University Hospital Muenster at 1 site in Germany.
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 1 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 2 Jul 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 Germany. 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 Johanna Raidt, MD (+49 251 83 40003, Johanna.Raidt@ukmuenster.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genotype-nasal Nitric Oxide Corelation (time frame: up to 20 years retrospective). 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 2 Jul 2021.