Primary Ciliary DyskinesiaEarly Phase 1NCT04901715
Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
A Early Phase 1 study testing Albuterol and Technetium99m - Sulfur Colloid (Tc99m-SC) in people with Primary Ciliary Dyskinesia, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. Read more about this study
- Who is it for?
- Ages 12 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Primary Ciliary Dyskinesia
- What is being tested?
- Albuterol and Technetium99m - Sulfur Colloid (Tc99m-SC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jun 2021to 22 Jul 2024
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 to 90 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Confirmed PCD diagnosis with identified genetic mutations
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
- Forced Expiratory Volume (FEV1) of at least 30 percent of predicted
- Age ≥ 18 years old
- Subjects must have an Forced vital capacity (FVC), Forced Expiratory Volume in one second (FEV1) and FVC/FEV1 of at least 80% of predicted.
- Subjects who fall out of the normal range will be offered a copy of the test to share with their personal physician.
- No pre-existing lung disease (asthma, cystic fibrosis, etc.).
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy.
Who cannot join
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, immunodeficiency, history of tuberculosis
- Any acute infection requiring antibiotics within 4 weeks of study.
- Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
- Medications which may impact the results of the study treatment, or may interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
- Active smoking to include e-cigarettes within 1 year of the study, or lifetime of > 10 pack years of smoking
- History of vaping or current vaping.
Show all 21Show fewer
- Viral upper respiratory tract infection within 4 weeks of challenge.
- Radiation exposure history in the past year which would be outside the safe levels
- Pregnant or lactating women will also be excluded since the risks associated with radiation are unknown and cannot be justified
- Use of the following medications:
- Use of beta blocking medications
- Receipt of Live Attenuated Influenza Vaccine (LAIV), also known as FluMist , within the prior 30 days, or any vaccine within the prior 5 days
- Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the treatment visit
- Non-steroidal anti-inflammatory drugs in the 4 days prior to the treatment visit.
- Allergy/sensitivity to study drugs or their formulations:
- Known Immunoglobulin E (IgE) mediated hypersensitivity to albuterol
- Physical/laboratory indications:
- Temperature > 37.8 degrees Celsius (C)
- Subjects >15 years- Systolic BP >150 mm hg or < 90 mm Hg or diastolic BP> 90 mm Hg or < 50 and Subjects 12-15 years - Systolic BP > 130 mmHg or < 80 mmHg or diastolic BP > 80 or <40
- Oxygen saturation of < 93 percent
- Inability or unwillingness of a participant to give written informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, 27514
About this study
The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype is a result of mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low, but significant rate of mucociliary clearance, while patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.
Read the detailed description
Participants will undergo screening with basic physical exam and lung function testing at the start of the study. Participants will then inhale a radiolabeled substance and undergo medical imaging to measure the clearance of mucus in the airways. Albuterol will be administered after the first imaging is completed. Lung function testing will be repeated. Finally, medical imaging will be repeated two more times to further look at clearance of mucus in the lungs. The study will be completed in one day and will last about 6 hours.
- Conditions
- Primary Ciliary Dyskinesia
- Being tested
- Albuterol, Technetium99m - Sulfur Colloid (Tc99m-SC)
- Keywords
- Mucociliary clearance, Radial Spoke Head Component 1 (RSPH1), Dynein Axonemal Heavy Chain 5 (DNAH5), albuterol, short acting beta-adrenergic (SABA), SABA
- 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.
AlbuterolDrug
Also called ProAir HFA hydrofluoroalkane (HFA) Inhaler, Ventolin HFA (hydrofluoroalkane) Inhaler
Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time.
Technetium99m - Sulfur Colloid (Tc99m-SC)Diagnostic test
Aerosolized radiolabeled Tc99m-sulfur colloid will be delivered using a modified Pari-LC Star nebulizer. The activity of Tc99m-SC loaded in the nebulizer will be adjusted to provide an estimated 40 microcurie (µCi) deposited in the lung for the MCC/CC scan. Patients between the age 12-18 years old will receive three quarters of the adult dose to account for the smaller lung volume.
| Study group | Role | What they receive |
|---|---|---|
| Genotypes associated mild phenotype | Active comparator | Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype. Receives: Drug: Albuterol; Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC) |
| Genotypes associated with severe phenotype | Active comparator | Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype. Receives: Drug: Albuterol; Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC) |
| Healthy Control | Active comparator | Healthy subjects with no pre-existing lung disease. Receives: Drug: Albuterol; Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes)
The average percent clearance in subjects with Primary Ciliary Dyskinesia (PCD) caused by mutations associated with mild and severe clinical phenotypes. Prior to each MCC study, a transmission Co57 scan will be performed to define the lung boundaries, to assign regions of interest, and to normalize these regions for lung volume differences. Radiolabeled Tc99m-sulfur colloid will be delivered using a modified Pari-LC Star nebulizer. The subject will then (within a minute of final inhalation maneuver) be seated in front of a large-field-of-view gamma camera to begin acquiring consecutive 2 minute images. The first two-2-minute images will provide initial, time zero activity (i.e. 100% retention) followed by the same imaging at the start of every 10-minute period until 1 hour has passed to assess baseline MCC. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time.
Measured: 60 minutes
Secondary outcomes (1)
Change in MCC (Ave120Clr-Ave60Clr;Average Clearance Between 60 and 120 Minutes)
The change in average percent clearance after the administration of albuterol in subjects with PCD caused by mutations associated with mild and severe clinical phenotypes PCD patients with mild disease compared to PCD patients with more severe disease. A transmission Cobalt57 scan will be performed to define the lung boundaries. Radiolabeled Tc99m-sulfur colloid (Technetium99m) will be delivered using a modified nebulizer. The subject will be seated in front of a large-field-of-view gamma camera to begin consecutive 2 minute images. The first two-2-minute images will provide initial, time zero activity followed by the same imaging at every 10-minute period until 1 hour. Subjects will then inhale 4 puffs of albuterol from the Metered Dose Inhaler (MDI) and consecutive 2 minute imaging continues for the next hour to assess the effect of albuterol on MCC. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time.
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2021
- Study start10 Jun 2021
- Primary completion22 Jul 2024
- Study completion22 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Ciliary DyskinesiaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Lawrence Ostrowski, PhD, Principal investigator, University of North Carolina at Chapel Hil
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04901715
- Sponsor's protocol ID
- 20-3465
- Other IDs
- R01HL117836
- Status last verified
- Aug 2025
- First submitted
- 19 May 2021
- Last updated
- 5 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual data that supports the results will be shared beginning 12 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
- ClinicalTrials.gov ID
- NCT04901715
- Acronym / sponsor ID
- 20-3465
- Conditions
- Primary Ciliary Dyskinesia
- Keywords
- Mucociliary clearance, Radial Spoke Head Component 1 (RSPH1), Dynein Axonemal Heavy Chain 5 (DNAH5), albuterol, short acting beta-adrenergic (SABA), SABA
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 25 May 2021 (actual)
- Results
- Posted 5 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype is a result of mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low, but significant rate of mucociliary clearance, while patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.
Detailed description
Participants will undergo screening with basic physical exam and lung function testing at the start of the study. Participants will then inhale a radiolabeled substance and undergo medical imaging to measure the clearance of mucus in the airways. Albuterol will be administered after the first imaging is completed. Lung function testing will be repeated. Finally, medical imaging will be repeated two more times to further look at clearance of mucus in the lungs. The study will be completed in one day and will last about 6 hours.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Genotypes associated mild phenotype | Active comparator | Drug: Albuterol, Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC)Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype. |
| Genotypes associated with severe phenotype | Active comparator | Drug: Albuterol, Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC)Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype. |
| Healthy Control | Active comparator | Drug: Albuterol, Diagnostic Test: Technetium99m - Sulfur Colloid (Tc99m-SC)Healthy subjects with no pre-existing lung disease. |
Who may qualify
- Ages
- 12 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed PCD diagnosis with identified genetic mutations
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
- Forced Expiratory Volume (FEV1) of at least 30 percent of predicted
- Age ≥ 18 years old
- Subjects must have an Forced vital capacity (FVC), Forced Expiratory Volume in one second (FEV1) and FVC/FEV1 of at least 80% of predicted.
Key exclusion criteria (21 listed)
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, immunodeficiency, history of tuberculosis
- Any acute infection requiring antibiotics within 4 weeks of study.
- Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
- Medications which may impact the results of the study treatment, or may interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
- Active smoking to include e-cigarettes within 1 year of the study, or lifetime of > 10 pack years of smoking
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 |
|---|---|---|
| AlbuterolAlso: ProAir HFA hydrofluoroalkane (HFA) Inhaler, Ventolin HFA (hydrofluoroalkane) InhalerAlbuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. | Drug | Genotypes associated mild phenotype, Genotypes associated with severe phenotype, Healthy Control |
| Technetium99m - Sulfur Colloid (Tc99m-SC)Aerosolized radiolabeled Tc99m-sulfur colloid will be delivered using a modified Pari-LC Star nebulizer. The activity of Tc99m-SC loaded in the nebulizer will be adjusted to provide an estimated 40 microcurie (µCi) deposited in the lung for the MCC/CC scan. Patients between the age 12-18 years old will receive three quarters of the adult dose to account for the smaller lung volume. | Diagnostic test | Genotypes associated mild phenotype, Genotypes associated with severe phenotype, Healthy Control |
Primary outcome
Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes)
Time frame: 60 minutes
The average percent clearance in subjects with Primary Ciliary Dyskinesia (PCD) caused by mutations associated with mild and severe clinical phenotypes. Prior to each MCC study, a transmission Co57 scan will be performed to define the lung boundaries, to assign regions of interest, and to normalize these regions for lung volume differences. Radiolabeled Tc99m-sulfur colloid will be delivered using a modified Pari-LC Star nebulizer. The subject will then (within a minute of final inhalation maneuver) be seated in front of a large-field-of-view gamma camera to begin acquiring consecutive 2 minute images. The first two-2-minute images will provide initial, time zero activity (i.e. 100% retention) followed by the same imaging at the start of every 10-minute period until 1 hour has passed to assess baseline MCC. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time.
1 secondary outcome
Change in MCC (Ave120Clr-Ave60Clr;Average Clearance Between 60 and 120 Minutes)
Time frame: 120 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Deidentified individual data that supports the results will be shared beginning 12 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
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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.
Lawrence Ostrowski, PhD principal investigator
University of North Carolina at Chapel Hil
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Albuterol and Technetium99m - Sulfur Colloid (Tc99m-SC) in people with Primary Ciliary Dyskinesia, run by University of North Carolina, Chapel Hill at 1 site in United States.
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 8 inclusion and 21 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: finished, as of the sponsor's last update on 5 Sep 2025. 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 United States. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes) (time frame: 60 minutes). 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 5 Sep 2025; AzTrials last refreshed its copy on 7 Nov 2026.