AsthmaPhase 4ENACTNCT03822637
The Effect of NAC on Lung Function and CT Mucus Score
A Phase 4 study testing n-acetylcystine + albuterol and 0.9% saline + albuterol in people with Asthma, run by University of California, San Francisco at 1 site in United States.
Trial summary
This study evaluates 20% n-acetylcysteine (NAC) in the treatment of moderate-to-severe asthma that is complicated by mucus in the airway, as determined by CT imaging. The study is a crossover design, which means that half the study participants will get 20% NAC in the first 14-day treatment period and placebo in the… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma
- What is being tested?
- n-acetylcystine + albuterol and 0.9% saline + albuterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Feb 2019to 21 Feb 2025
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female between the ages of 18 and 80 years of age at Visit 1
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
- Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine provocative concentration that results in a 20% fall in FEV1(PC20) ≤ 16 mg/mL)
- Clinical history of asthma per patient report or medical record
- Pre-bronchodilator FEV1 > 35% predicted
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- Post-bronchodilator FEV1 > 40% but < 90% predicted
- Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater
- CT mucus score ≥ 5
- Ability to tolerate study drug reflected by a post-treatment FEV1 ≥ 80% of pre- treatment, pre-bronchodilator FEV1
Who cannot join
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
- Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year smoking history
- Adherence to study drug ≤ 70% after first treatment period
- Current participation in an investigational drug trial
- Other chronic pulmonary disorders, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and at the PI's discretion), severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways
Show all 9Show fewer
- Unwillingness to follow study procedures
- History of allergy or intolerance to study drug
- Any other criteria that places the subject at unnecessary risk according to the judgment of the Principal Investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Airway Clinical Research Center
San Francisco, California, 94143
About this study
This study evaluates 20% n-acetylcysteine (NAC) in the treatment of moderate-to-severe asthma that is complicated by mucus in the airway, as determined by CT imaging. The study is a crossover design, which means that half the study participants will get 20% NAC in the first 14-day treatment period and placebo in the next 14-day treatment period; and the other half will get placebo in the first 14-day treatment period and 20% NAC in the next 14-day treatment period.
Read the detailed description
N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus. Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a factor in chronic severe asthma as well. This role has been hard to prove because of difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a majority of people with severe asthma have at least one lung segment with a mucus plug and 27% have more than four lung segments with mucus plugs.
Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive lung diseases, like Chronic Obstructive Pulmonary Disease (COPD). However, utilizing CT mucus scores as a biomarker, investigators believe that mucolytic treatment may prove useful for those with significant mucus impaction.
This is a randomized, double-blind, placebo-controlled phase 4 study of 20% NAC in patients with asthma who also have evidence of mucus in their lungs as determined by CT imaging. Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus in the airways, with a mucolytic like NAC, will result in an improvement of lung function.
- Conditions
- Asthma
- Being tested
- n-acetylcystine + albuterol, 0.9% saline + albuterol
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
n-acetylcystine + albuterolCombination product
Also called Mucomyst, NAC, n-acetylcystine
NAC (trade name: Mucomyst) is a mucolytic drug manufactured by American Regent. The active drug studied here is 20% NAC (3 mL) and 2.5 mg albuterol bronchodilator inhalation solution (0.5 mL).
0.9% saline + albuterolCombination product
Also called Normal saline
The placebo comparator in this study is 0.9% normal saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL).
| Study group | Role | What they receive |
|---|---|---|
| 20% n-acetylcystine (NAC) | Experimental | Participants will self-administer nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 14 days. Receives: Combination Product: n-acetylcystine + albuterol |
| 0.9% saline | Placebo comparator | Participants will self-administer nebulized 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 14 days. Receives: Combination Product: 0.9% saline + albuterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Liters at 2 Weeks
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.
Measured: Baseline and 2 Weeks
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Percent Predicted at 2 Weeks
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.
Measured: Baseline and 2 Weeks
Secondary outcomes (8)
Mucus Plug Segment Score
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.
Measured: 2 Weeks
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Liters at 2 Weeks
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.
Measured: 2 Weeks
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Percent Predicted at 2 Weeks
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.
Measured: 2 Weeks
Air Trapping
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.
Measured: 2 Weeks
Fractional Exhaled Nitric Oxide Level (FeNO)
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.
Measured: 2 Weeks
Absolute Eosinophil Count
Absolute eosinophil count is measured through blood tests. The absolute change in absolute eosinophil count at 2 weeks was calculated.
Measured: 2 Weeks
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Liters/Second (L/s) at 2 Weeks
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.
Measured: 2 Weeks
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Percent Predicted at 2 Weeks
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.
Measured: 2 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2019
- Study start20 Feb 2019
- Primary completion21 Feb 2025
- Study completion21 Feb 2025
Why it stopped: The study was terminated due to COVID restrictions and funding challenges. The study was then simplified and redesigned as the TEAM study (NCT06152653).
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Fahy, M.D, M.Sc., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03822637
- Sponsor's protocol ID
- 18-26680
- Acronym
- ENACT
- Status last verified
- May 2026
- First submitted
- 14 Dec 2018
- Last updated
- 11 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9. doi: 10.1016/s0002-9343(03)00260-2. No abstract available.
PubMed 12867239DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13(1):27-33. doi: 10.1136/jcp.13.1.27.
PubMed 13818688
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of NAC on Lung Function and CT Mucus Score
- ClinicalTrials.gov ID
- NCT03822637
- Acronym / sponsor ID
- ENACT / 18-26680
- Conditions
- Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to COVID restrictions and funding challenges. The study was then simplified and redesigned as the TEAM study (NCT06152653).
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 20 Feb 2019 (actual)
- Primary completion
- 21 Feb 2025 (actual)
- Study completion
- 21 Feb 2025 (actual)
- First posted
- 30 Jan 2019 (actual)
- Results
- Posted 11 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates 20% n-acetylcysteine (NAC) in the treatment of moderate-to-severe asthma that is complicated by mucus in the airway, as determined by CT imaging. The study is a crossover design, which means that half the study participants will get 20% NAC in the first 14-day treatment period and placebo in the next 14-day treatment period; and the other half will get placebo in the first 14-day treatment period and 20% NAC in the next 14-day treatment period.
Detailed description
N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus. Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a factor in chronic severe asthma as well. This role has been hard to prove because of difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a majority of people with severe asthma have at least one lung segment with a mucus plug and 27% have more than four lung segments with mucus plugs.
Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive lung diseases, like Chronic Obstructive Pulmonary Disease (COPD). However, utilizing CT mucus scores as a biomarker, investigators believe that mucolytic treatment may prove useful for those with significant mucus impaction.
This is a randomized, double-blind, placebo-controlled phase 4 study of 20% NAC in patients with asthma who also have evidence of mucus in their lungs as determined by CT imaging. Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus in the airways, with a mucolytic like NAC, will result in an improvement of lung function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 20% n-acetylcystine (NAC) | Experimental | Combination Product: n-acetylcystine + albuterolParticipants will self-administer nebulized 20% NAC (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 14 days. |
| 0.9% saline | Placebo comparator | Combination Product: 0.9% saline + albuterolParticipants will self-administer nebulized 0.9% saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL) 3 times per day for 14 days. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female between the ages of 18 and 80 years of age at Visit 1
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
- Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine provocative concentration that results in a 20% fall in FEV1(PC20) ≤ 16 mg/mL)
- Clinical history of asthma per patient report or medical record
Key exclusion criteria (9 listed)
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
- Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
- Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year smoking history
- Adherence to study drug ≤ 70% after first treatment period
- Current participation in an investigational drug trial
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 |
|---|---|---|
| n-acetylcystine + albuterolAlso: Mucomyst, NAC, n-acetylcystineNAC (trade name: Mucomyst) is a mucolytic drug manufactured by American Regent. The active drug studied here is 20% NAC (3 mL) and 2.5 mg albuterol bronchodilator inhalation solution (0.5 mL). | Combination product | 20% n-acetylcystine (NAC) |
| 0.9% saline + albuterolAlso: Normal salineThe placebo comparator in this study is 0.9% normal saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL). | Combination product | 0.9% saline |
Primary outcome
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Liters at 2 Weeks
Time frame: Baseline and 2 Weeks
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.
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Percent Predicted at 2 Weeks
Time frame: Baseline and 2 Weeks
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.
8 secondary outcomes
Mucus Plug Segment Score
Time frame: 2 Weeks
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Liters at 2 Weeks
Time frame: 2 Weeks
Percent Change From Baseline in Mean Forced Vital Capacity (FVC) Percent Predicted at 2 Weeks
Time frame: 2 Weeks
Air Trapping
Time frame: 2 Weeks
Fractional Exhaled Nitric Oxide Level (FeNO)
Time frame: 2 Weeks
Absolute Eosinophil Count
Time frame: 2 Weeks
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Liters/Second (L/s) at 2 Weeks
Time frame: 2 Weeks
Percent Change From Baseline in Mean Peak Expiratory Flow (PEF) Percent Predicted at 2 Weeks
Time frame: 2 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12867239Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9. doi: 10.1016/s0002-9343(03)00260-2. No abstract available.
- Background: PubMed 13818688DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13(1):27-33. doi: 10.1136/jcp.13.1.27.
- Individual participant dataSharing planned: No
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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.
John Fahy, M.D, M.Sc. principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing n-acetylcystine + albuterol and 0.9% saline + albuterol in people with Asthma, run by University of California, San Francisco 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 10 inclusion and 9 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: stopped early, as of the sponsor's last update on 11 Jun 2026. 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. Some participants in this study may receive a placebo. 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?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 11 Jun 2026). 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?
Percent Change From Baseline in Mean Forced Expiratory Volume in One Second (FEV1) Liters at 2 Weeks (time frame: Baseline and 2 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03822637, which also lists 2 linked publications.
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 11 Jun 2026.