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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL117836 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Healthy Control | Active Comparator | Healthy subjects with no pre-existing lung disease. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albuterol | Drug | Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 60 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cough Clearance (Ave150Clr-Ave120Clr; Average Clearance Between 120 and 150 Minutes) | The change in average percent of cough clearance 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. After completion of baseline MCC measurement and post-Albuterol MCC measurement. Subjects will cough a total of 30 times over a 30-minute period to assess cough clearance by gamma imaging over that period. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time. |
Inclusion Criteria for PCD Patients
Inclusion Criteria for Healthy Controls:
Subjects who fall out of the normal range will be offered a copy of the test to share with their personal physician.
Exclusion Criteria:
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.
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:
Allergy/sensitivity to study drugs or their formulations:
Known Immunoglobulin E (IgE) mediated hypersensitivity to albuterol
Physical/laboratory indications:
Inability or unwillingness of a participant to give written informed consent.
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| Name | Affiliation | Role |
|---|---|---|
| Lawrence Ostrowski, PhD | University of North Carolina at Chapel Hil | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina Chapel Hill | Chapel Hill | North Carolina | 27514 | United States |
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.
12-36 months following publication
Investigators with IRB, IEC, or REB approval and an executed data use/sharing agreement with UNC.
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Of the 27 participants who signed informed consent, three participants failed screening and were ineligible to continue participation and did not receive the study intervention.
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| ID | Title | Description |
|---|---|---|
| FG000 | Genotypes Associated With Mild Phenotype | Subjects with 2 confirmed mutations in Radial Spoke Head Component 1 (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. Albuterol: Albuterol HFA hydrofluoroalkane (HFA) Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 mucociliary clearance cough clearance (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. |
| FG001 | Genotypes Associated With Severe Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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. |
| FG002 | Healthy Control | Healthy subjects with no pre-existing lung disease. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Genotypes Associated With Mild Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One participant was originally included in the Genotypes Associated with Mild Phenotype Arm based on available knowledge. Upon further study of the genotype, it was concluded that this participant did not meet the criteria for a mild phenotype and was therefore excluded from the analysis. | Posted | Median | Inter-Quartile Range | percent clearance | 60 minutes |
From the time of signing informed consent through 96 hours after completion of the single 8-hour study visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Genotypes Associated With Mild Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kelli Sullivan, MPH | University of North Carolina at Chapel Hill | 919-962-9786 | kelli_sullivan@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 8, 2023 | Aug 15, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 27, 2023 | Aug 15, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D002925 | Ciliary Motility Disorders |
| ID | Term |
|---|---|
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D000072661 | Ciliopathies |
| D000015 | Abnormalities, Multiple |
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Not provided
| ID | Term |
|---|---|
| D000420 | Albuterol |
| D009330 | Nebulizers and Vaporizers |
| C094049 | apaflurane |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
Not provided
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Not provided
Not provided
Not provided
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Not provided
|
| 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. |
|
| 120 minutes |
| 150 minutes |
| BG001 | Genotypes Associated With Severe Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| BG002 | Healthy Control | Healthy subjects with no pre-existing lung disease. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Genotypes Associated With Mild Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| OG001 | Genotypes Associated With Severe Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
| OG002 | Healthy Control | Healthy subjects with no pre-existing lung disease. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. |
|
|
|
| Secondary | 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. | One participant was originally included in the Genotypes Associated with Mild Phenotype Arm based on available knowledge. Upon further study of the genotype, it was concluded that this participant did not meet the criteria for a mild phenotype and was therefore excluded from the analysis. | Posted | Median | Inter-Quartile Range | percent clearance | 120 minutes |
|
|
|
|
| Other Pre-specified | Change in Cough Clearance (Ave150Clr-Ave120Clr; Average Clearance Between 120 and 150 Minutes) | The change in average percent of cough clearance 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. After completion of baseline MCC measurement and post-Albuterol MCC measurement. Subjects will cough a total of 30 times over a 30-minute period to assess cough clearance by gamma imaging over that period. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time. | Not Posted | 150 minutes | Participants |
| 0 |
| 8 |
| 0 |
| 8 |
| 0 |
| 8 |
| EG001 | Genotypes Associated With Severe Phenotype | 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. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. | 0 | 8 | 0 | 8 | 0 | 8 |
| EG002 | Healthy Control | Healthy subjects with no pre-existing lung disease. Albuterol: Albuterol HFA Metered Dose Inhaler (90mcg/puff). Subjects to use 4 puffs one time. 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 ¾ of the adult dose to account for the smaller lung volume. | 0 | 8 | 0 | 8 | 0 | 8 |
Not provided
Not provided
Not provided
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D000588 |
| Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D004864 | Equipment and Supplies |
| Other |
| ANOVA | 0.58 | Other |