Nasal Nitric Oxide Test for Primary Ciliary Dyskinesia

(PCD Trial)

Overseen By Sigrid M Almeida, BS

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Connecticut Children's Medical Center

Must not be taking: Antibiotics

Disqualifiers: Sinus surgery, Bloody nose, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new nasal test, called Nasal Nitric Oxide testing, in diagnosing primary ciliary dyskinesia (PCD). PCD affects breathing due to issues with tiny hair-like structures in the airways. The test measures nitric oxide levels in the nose, which are typically lower in individuals with PCD. Those with symptoms such as chronic cough, a constantly runny nose, or neonatal breathing issues may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the test's performance in an initial, smaller group, offering participants a chance to contribute to early-stage diagnostic advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently being treated with antibiotics for sinusitis or a respiratory issue, you may not be eligible to participate.

What prior data suggests that nasal nitric oxide testing is safe?

Research shows that nasal nitric oxide (nNO) testing is safe and easy to perform. Studies have found it to be an effective and accurate method for diagnosing primary ciliary dyskinesia (PCD), a condition characterized by low levels of nitric oxide in the sinuses. As a non-invasive test, it avoids surgery or needles, ensuring patient comfort. No reports of serious side effects from nNO testing exist, so it is considered safe for individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Nasal Nitric Oxide test for Primary Ciliary Dyskinesia (PCD) because it offers a non-invasive, quick, and reliable method for diagnosing this rare lung condition. Unlike traditional diagnosis methods, which often involve more invasive procedures like ciliary biopsies or extensive genetic testing, nasal nitric oxide testing provides results rapidly and with minimal discomfort. This approach could streamline the diagnostic process, allowing patients to begin appropriate management sooner, which is crucial in managing PCD effectively.

What evidence suggests that nasal nitric oxide testing is effective for diagnosing primary ciliary dyskinesia?

Research shows that testing for nasal nitric oxide (nNO) aids in diagnosing primary ciliary dyskinesia (PCD), a rare genetic disorder affecting tiny hair-like structures in the airways. Studies have found that people with PCD usually exhibit very low nNO levels. This makes nNO testing a useful and non-invasive method for detecting the condition, allowing doctors to identify PCD without more invasive tests. While more everyday clinical data is needed, current research supports nNO testing as an effective diagnostic tool for PCD. Participants in this trial will undergo nNO testing to further evaluate its effectiveness in diagnosing PCD. ^{3 4 6 7 8}

Who Is on the Research Team?

Melanie S Collins, MD

Principal Investigator

Connecticut Children's Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 2 years or older who may have primary ciliary dyskinesia (PCD). They should have symptoms like neonatal respiratory distress, chronic nasal issues, coughing, organ placement anomalies, or bronchiectasis. It's not for those currently hospitalized with respiratory issues, on antibiotics for sinusitis/respiratory problems, unable to tolerate a nasal probe, or unable to consent.

Inclusion Criteria

I have at least two symptoms like chronic cough or nasal issues.

I am at least 2 years old.

Ability to provide informed consent or consent of parent/guardian and ass

Exclusion Criteria

The study doctors think you may not be a good fit for the testing for any other reason.

I understand the study requirements and am willing to sign the consent form.

I am currently taking antibiotics for sinusitis or another respiratory issue.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Nasal Nitric Oxide Testing

Participants undergo nasal nitric oxide testing and clinical information regarding prior diagnostic testing is collected

1 visit

1 visit (in-person)

Data Collection and Registry Enrollment

Participants are enrolled in the Nasal NO REDCap registry and data is collected for evaluation of PCD diagnostic testing utility

2-3 years

Follow-up

Participants are monitored for refinement and improvement of PCD diagnostic testing processes

1-2 years

What Are the Treatments Tested in This Trial?

Interventions

• Nasal Nitric Oxide testing

Trial Overview

The study is testing the effectiveness of nasal nitric oxide testing as a diagnostic tool for PCD. This non-invasive test measures nitric oxide in the sinuses; low levels are typical in PCD patients. The goal is to collect data from regular clinical use and improve diagnosis methods.

How Is the Trial Designed?

Group I: Nasal Nitric Oxide Experimental Treatment 1 Intervention

Participants who are referred by his/her clinician for nasal NO testing and meet the inclusion and exclusion criteria will undergo testing. Clinical information regarding prior diagnostic testing will be collected at time of enrollment. Participants that have a confirmed diagnosis of PCD by genetics or ciliary biopsy at time of study entry

Who Is Running the Clinical Trial?

Connecticut Children's Medical Center

Lead Sponsor

Trials

76

Recruited

30,000+

UConn Health

Collaborator

Trials

218

Recruited

59,100+

Published Research Related to This Trial

Nasal nitric oxide levels are significantly low in patients with primary ciliary dyskinesia (PCD), making its measurement a recommended diagnostic test for patients aged 5 and older.

To ensure accurate results, nasal nitric oxide testing must be conducted using standardized protocols and chemiluminescence analyzers, with repeat testing necessary to confirm persistent low levels indicative of PCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols. Shapiro, AJ., Dell, SD., Gaston, B., et al.[2021]

Nasal nitric oxide (nNO) measurement is feasible in healthy newborns during natural sleep, achieving a 100% success rate for at least one nostril using a chemoluminescence device, although lower success rates were observed with an electrochemical device.

The median nNO concentration in neonates was significantly lower than in older individuals, suggesting that using nNO levels for screening primary ciliary dyskinesia (PCD) in the first week of life may not be effective, and alternative diagnostic methods should be considered if PCD is suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of nasal NO screening in healthy newborns. Buechel, F., Usemann, J., Aline, A., et al.[2022]

A standardized protocol for measuring nasal nitric oxide (nNO) established a disease-specific cutoff value of 77 nl/min, which accurately identifies individuals with primary ciliary dyskinesia (PCD) with a sensitivity of 98% and specificity greater than 99%.

In a multicenter validation involving 155 individuals suspected of having PCD, this cutoff successfully identified 98.6% of participants with confirmed PCD, demonstrating the test's efficacy and reliability for clinical diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. Leigh, MW., Hazucha, MJ., Chawla, KK., et al.[2022]

Nasal nitric oxide (nNO) levels were significantly lower in children with primary ciliary dyskinesia (PCD) compared to those with asthma, post-infectious bronchiolitis obliterans, and non-PCD/non-CF bronchiectasis, establishing a potential diagnostic marker for PCD.

A cut-off nNO value of 76 nL/min showed high sensitivity (86.1%) and specificity (91.4%) for diagnosing PCD in Chinese children, indicating that nNO testing can effectively differentiate PCD from other respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of nasal nitric oxide measurement in the diagnosis of primary ciliary dyskinesia. Zhang, X., Wang, X., Li, H., et al.[2022]

A study involving 85 children (20 with primary ciliary dyskinesia (PCD) and 65 controls) found that various non-invasive breathing techniques for measuring nasal nitric oxide (nNO) can effectively distinguish PCD from other conditions, achieving 100% sensitivity and over 90% specificity.

While all techniques were reproducible and valid for diagnosing PCD, they produced lower nNO values compared to the standard exhalation against resistance method, indicating that while easier methods are effective, they may require adjusted cutoff values for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia. Mateos-Corral, D., Coombs, R., Grasemann, H., et al.[2019]

Patients with primary ciliary dyskinesia (PCD) showed significantly lower nasal nitric oxide (nNO) levels compared to healthy controls across all measurement methods, indicating a potential diagnostic marker for PCD.

The study demonstrated that nNO measurements, regardless of the method used (aspiration, exhalation, or humming), consistently exhibited excellent specificity and sensitivity for detecting PCD, supporting the idea of defective nitric oxide production in the paranasal sinuses of affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal nitric oxide assessment in primary ciliary dyskinesia using aspiration, exhalation, and humming. Santamaria, F., De Stefano, S., Montella, S., et al.[2018]

Citations

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pmc.ncbi.nlm.nih.gov

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Nasal nitric oxide measurement for the diagnosis of ...

Nasal nitric oxide (nNO) measurement is important in the primary ciliary dyskinesia (PCD) diagnostic pathway because levels are consistently very low in most ...

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publications.ersnet.org/content/erj/44/6/1589

Nasal nitric oxide screening for primary ciliary dyskinesia

Abstract. Nasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test.

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clinicaltrials.gov

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Nasal Nitric Oxide Across Mutations in Primary Ciliary ...

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by dysfunction of motile cilia associated with recurrent infections of the airways ...

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mdpi.com/1422-0067/24/22/16159

Role of Nasal Nitric Oxide in Primary Ciliary Dyskinesia ...

We conducted a narrative review of the literature to examine the relationship between nNO and some respiratory diseases with a particular focus on primary ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3960971/

Standardizing Nasal Nitric Oxide Measurement as a Test for ...

Rationale: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6993796/

Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia ...

Meta-analyses and prospective cohort studies support nNO testing as a safe, noninvasive, feasible, and accurate PCD diagnostic test (3–6). However, nNO testing ...

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niox.com

niox.com/en/nno-pcd/primary-ciliary-dyskinesia/

Nasal Nitric Oxide (nNO) and Primary Ciliary Dyskinesia ...

nNO is substantially diminished in some conditions, such as Primary Ciliary Dyskinesia (PCD), making nNO a useful biomarker for supporting diagnosis.

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iopscience.iop.org

iopscience.iop.org/article/10.1088/1752-7163/ad10f9

Device comparison study to measure nasal nitric oxide in ...

This study aimed to compare nNO measurement using three different devices in distinguishing PCD patients from healthy controls and cystic fibrosis (CF) ...