Trial Outcomes & Findings for The Effect of NAC on Lung Function and CT Mucus Score (NCT NCT03822637)
NCT ID: NCT03822637
Last Updated: 2026-06-11
Results Overview
FEV1 Liters was assessed with participants in a seated position. FEV1 Liters was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean FEV1 Liters from baseline to 2 weeks after treatment was calculated.
TERMINATED
PHASE4
4 participants
Baseline and 2 Weeks
2026-06-11
Participant Flow
28 participants were screened for eligibility between February 2019 and March 2020 at the University of California, San Francisco (UCSF) Airway Clinical Research Center in San Francisco, California.
4 of 28 participants were randomized. Of those not randomized, 22 did not meet inclusion criteria and 2 declined to participate.
Participant milestones
| Measure |
Experimental: N-Acetylcysteine (NAC), Then Placebo
Participants first self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
Experimental: Placebo, Then NAC
Participants first self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
|---|---|---|
|
First Intervention (2 Weeks)
STARTED
|
2
|
2
|
|
First Intervention (2 Weeks)
Received Intervention
|
2
|
2
|
|
First Intervention (2 Weeks)
COMPLETED
|
2
|
2
|
|
First Intervention (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Washout (8 Weeks)
STARTED
|
2
|
2
|
|
Washout (8 Weeks)
COMPLETED
|
2
|
2
|
|
Washout (8 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (2 Weeks)
STARTED
|
2
|
2
|
|
Second Intervention (2 Weeks)
COMPLETED
|
2
|
0
|
|
Second Intervention (2 Weeks)
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Experimental: N-Acetylcysteine (NAC), Then Placebo
Participants first self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
Experimental: Placebo, Then NAC
Participants first self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
|---|---|---|
|
Second Intervention (2 Weeks)
Adverse Event
|
0
|
2
|
Baseline Characteristics
The Effect of NAC on Lung Function and CT Mucus Score
Baseline characteristics by cohort
| Measure |
Experimental: NAC, Then Placebo
n=2 Participants
Participants first self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
Experimental: Placebo, Then NAC
n=2 Participants
Participants first self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks. After a washout period of 8 weeks, they then self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=20 Participants
|
2 Participants
n=20 Participants
|
4 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=20 Participants
|
1 Participants
n=20 Participants
|
2 Participants
n=40 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=20 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=40 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=20 Participants
|
2 participants
n=20 Participants
|
4 participants
n=40 Participants
|
|
Forced Expiratory Volume in One Second (FEV1) Measurement
|
55.70 Percent Predicted
STANDARD_DEVIATION 0.09 • n=20 Participants
|
65.60 Percent Predicted
STANDARD_DEVIATION 0.02 • n=20 Participants
|
60.65 Percent Predicted
STANDARD_DEVIATION 0.08 • n=40 Participants
|
PRIMARY outcome
Timeframe: Baseline and 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
FEV1 Liters was assessed with participants in a seated position. FEV1 Liters was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean FEV1 Liters from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Liters at 2 Weeks
|
-9.84 Percent change
Standard Deviation 6.49
|
-3.02 Percent change
Standard Deviation 3.74
|
PRIMARY outcome
Timeframe: Baseline and 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
FEV1 percent predicted was assessed with participants in a seated position. FEV1 percent predicted was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean FEV1 percent predicted from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Percent Predicted at 2 Weeks
|
-9.89 Percent change
Standard Deviation 6.59
|
-2.95 Percent change
Standard Deviation 4.16
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
Participants completed a chest computed tomography (CT) scan at the start and end of each 2-week treatment period. Two radiologists independently reviewed each CT scan to determine the number of mucus-plugged bronchopulmonary segments present in the scan, ranging from 0 to 20. A higher number of mucus-plugged bronchopulmonary segments indicates a greater number of mucus plugs. The absolute change in mucus-plugged segments at 2 weeks was reported.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Mucus Plug Segment Score
|
1 Mucus-plugged segments
Standard Deviation 2
|
0 Mucus-plugged segments
Standard Deviation 4
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
FVC Liters was assessed with participants in a seated position. FVC Liters was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean FVC Liters from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Liters at 2 Weeks
|
-4.12 Percent change
Standard Deviation 3.85
|
-2.01 Percent change
Standard Deviation 6.36
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
FVC percent predicted was assessed with participants in a seated position. FVC percent predicted was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean FVC percent predicted from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Percent Predicted at 2 Weeks
|
-3.99 Percent change
Standard Deviation 3.87
|
-1.99 Percent change
Standard Deviation 6.40
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
Air trapping is measured as the ratio of residual volume (RV) to total lung capacity (TLC). The absolute change in air trapping at 2 weeks was calculated. The RV and TLC are measured through body plethysmography.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Air Trapping
|
0.01 Ratio
Standard Deviation 0.03
|
-0.02 Ratio
Standard Deviation 0.04
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
FeNO is measured as the concentration of nitric oxide in the air exhaled by each participant into an inhaled nitric oxide machine. The absolute change in FeNO levels at 2 weeks was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Fractional Exhaled Nitric Oxide Level (FeNO)
|
2 Parts per billion (ppb)
Standard Deviation 24
|
16 Parts per billion (ppb)
Standard Deviation 35
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
Absolute eosinophil count is measured through blood tests. The absolute change in absolute eosinophil count at 2 weeks was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Absolute Eosinophil Count
|
0.08 cells x 10^9/L
Standard Deviation 0.13
|
0.16 cells x 10^9/L
Standard Deviation 0.39
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
PEF Liters/second was assessed with participants in a seated position. PEF L/s was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean PEF L/s from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Liters/Second (L/s) at 2 Weeks
|
-6.07 Percent change
Standard Deviation 5.37
|
-6.09 Percent change
Standard Deviation 5.97
|
SECONDARY outcome
Timeframe: 2 WeeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis.
PEF percent predicted was assessed with participants in a seated position. PEF percent predicted was measured with a PC-based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. The percent change in mean PEF percent predicted from baseline to 2 weeks after treatment was calculated.
Outcome measures
| Measure |
Placebo
n=4 Participants
Participants who self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
20% N-Acetylcysteine (NAC)
n=4 Participants
Participants who self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks in either the first or last 2 weeks of the study.
|
|---|---|---|
|
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Percent Predicted at 2 Weeks
|
-6.12 Percent change
Standard Deviation 5.38
|
-6.06 Percent change
Standard Deviation 6.02
|
Adverse Events
20% N-Acetylcysteine (NAC)
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
20% N-Acetylcysteine (NAC)
n=4 participants at risk
Participants self-administered nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
Placebo
n=4 participants at risk
Participants first self-administered the nebulized NAC-matched Placebo of 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 2 weeks.
|
|---|---|---|
|
General disorders
Headache
|
50.0%
2/4 • Number of events 2 • From enrollment until the end of follow-up, up to 16 weeks
Adverse events (AEs) will be monitored in real time by the Clinical Principal Investigators (Drs. Fahy, Woodruff, and Lazarus). In addition, AEs will be reviewed quarterly during the regularly scheduled quality assurance meetings of the UCSF Airway Clinical Research Center, which are attended by Drs. Fahy, Woodruff, and Lazarus, as well as an external UCSF patient safety officer. Additionally, serious adverse events will be reported to the UCSF Institutional Review Board as required.
|
0.00%
0/4 • From enrollment until the end of follow-up, up to 16 weeks
Adverse events (AEs) will be monitored in real time by the Clinical Principal Investigators (Drs. Fahy, Woodruff, and Lazarus). In addition, AEs will be reviewed quarterly during the regularly scheduled quality assurance meetings of the UCSF Airway Clinical Research Center, which are attended by Drs. Fahy, Woodruff, and Lazarus, as well as an external UCSF patient safety officer. Additionally, serious adverse events will be reported to the UCSF Institutional Review Board as required.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation
|
50.0%
2/4 • Number of events 2 • From enrollment until the end of follow-up, up to 16 weeks
Adverse events (AEs) will be monitored in real time by the Clinical Principal Investigators (Drs. Fahy, Woodruff, and Lazarus). In addition, AEs will be reviewed quarterly during the regularly scheduled quality assurance meetings of the UCSF Airway Clinical Research Center, which are attended by Drs. Fahy, Woodruff, and Lazarus, as well as an external UCSF patient safety officer. Additionally, serious adverse events will be reported to the UCSF Institutional Review Board as required.
|
0.00%
0/4 • From enrollment until the end of follow-up, up to 16 weeks
Adverse events (AEs) will be monitored in real time by the Clinical Principal Investigators (Drs. Fahy, Woodruff, and Lazarus). In addition, AEs will be reviewed quarterly during the regularly scheduled quality assurance meetings of the UCSF Airway Clinical Research Center, which are attended by Drs. Fahy, Woodruff, and Lazarus, as well as an external UCSF patient safety officer. Additionally, serious adverse events will be reported to the UCSF Institutional Review Board as required.
|
Additional Information
Dr. John V. Fahy
University of California, San Francisco
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place