Trial Outcomes & Findings for Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype (NCT NCT04901715)
NCT ID: NCT04901715
Last Updated: 2025-09-05
Results Overview
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.
COMPLETED
EARLY_PHASE1
27 participants
60 minutes
2025-09-05
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
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|---|---|---|---|
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Overall Study
STARTED
|
10
|
8
|
9
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
Baseline characteristics by cohort
| Measure |
Genotypes Associated With Mild Phenotype
n=8 Participants
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.
|
Genotypes Associated With Severe Phenotype
n=8 Participants
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.
|
Healthy Control
n=8 Participants
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.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 60 minutesPopulation: 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.
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.
Outcome measures
| Measure |
Genotypes Associated With Mild Phenotype
n=7 Participants
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.
|
Genotypes Associated With Severe Phenotype
n=8 Participants
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.
|
Healthy Control
n=8 Participants
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.
|
|---|---|---|---|
|
Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes)
|
1.4 percent clearance
Interval -0.42 to 2.6
|
-1.1 percent clearance
Interval -1.3 to 2.7
|
7.3 percent clearance
Interval 4.9 to 9.1
|
SECONDARY outcome
Timeframe: 120 minutesPopulation: 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.
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.
Outcome measures
| Measure |
Genotypes Associated With Mild Phenotype
n=7 Participants
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.
|
Genotypes Associated With Severe Phenotype
n=8 Participants
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.
|
Healthy Control
n=8 Participants
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.
|
|---|---|---|---|
|
Change in MCC (Ave120Clr-Ave60Clr;Average Clearance Between 60 and 120 Minutes)
|
0.82 percent clearance
Interval -0.53 to 1.9
|
-0.42 percent clearance
Interval -1.4 to 2.5
|
9.7 percent clearance
Interval 1.82 to 12.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 150 minutesThe 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.
Outcome measures
Outcome data not reported
Adverse Events
Genotypes Associated With Mild Phenotype
Genotypes Associated With Severe Phenotype
Healthy Control
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Kelli Sullivan, MPH
University of North Carolina at Chapel Hill
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place