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

Trial Summary

What is the purpose of this trial?

This cross-sectional and longitudinal observational study is to gather data on the utility of tests that are used to make a diagnosis of primary ciliary dyskinesia (PCD). There is new testing available, called nasal nitric oxide testing, that non-invasively measures nitric oxide levels in the sinus cavity. Individuals with PCD characteristically have low levels, but this testing does not have extensive data from everyday clinical practice. The objective of this proposal is to improve the diagnostic approach to children and adults with clinical concerns for primary ciliary dyskinesia (PCD).

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 data supports the effectiveness of the treatment Nasal Nitric Oxide testing for Primary Ciliary Dyskinesia?

Research shows that people with primary ciliary dyskinesia (PCD) have very low levels of nasal nitric oxide (nNO), making nNO measurement a useful test to help diagnose PCD. This test is recommended for patients aged 5 and older, and when done correctly, it provides reliable results. ^{1 2 3 4 5}

Is nasal nitric oxide testing safe for humans?

Nasal nitric oxide testing is a non-invasive method used to diagnose primary ciliary dyskinesia and is generally considered safe for humans, including children aged 5 years and older, when performed using standardized protocols. ^{1 2 3 4 6}

How is the nasal nitric oxide test treatment for primary ciliary dyskinesia different from other treatments?

The nasal nitric oxide test is unique because it is a diagnostic tool rather than a treatment, used to measure the levels of nitric oxide in the nose, which are typically low in people with primary ciliary dyskinesia. This test is non-invasive and helps in diagnosing the condition by using different methods like aspiration, exhalation, and humming to measure nitric oxide levels. ^{1 2 3 4 5}

Research Team

Melanie S Collins, MD

Principal Investigator

Connecticut Children's Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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) 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Feasibility of nasal NO screening in healthy newborns. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The value of nasal nitric oxide measurement in the diagnosis of primary ciliary dyskinesia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Nasal Nitric Oxide Measurement in Primary Ciliary Dyskinesia. A Technical Paper on Standardized Testing Protocols. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Nasal nitric oxide assessment in primary ciliary dyskinesia using aspiration, exhalation, and humming. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Diagnostic value of nasal nitric oxide measured with non-velum closure techniques for children with primary ciliary dyskinesia. [2019]