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The study was terminated due to COVID restrictions and funding challenges. The study was then simplified and redesigned as the TEAM study (NCT06152653).
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| n-acetylcystine + albuterol | Combination Product | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline and 2 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Fahy, M.D, M.Sc. | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Airway Clinical Research Center | San Francisco | California | 94143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12867239 | Background | 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. | |
| 13818688 | Background | DUNNILL 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. |
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4 of 28 participants were randomized. Of those not randomized, 22 did not meet inclusion criteria and 2 declined to participate.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (2 Weeks) |
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| Washout (8 Weeks) |
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| Second Intervention (2 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental: 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. |
| 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 | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | Baseline and 2 Weeks |
|
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.
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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 | 20% N-Acetylcysteine (NAC) | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John V. Fahy | University of California, San Francisco | 415-476-9940 | john.fahy@ucsf.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 | May 26, 2021 | Feb 4, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| C030905 | N-monoacetylcystine |
| D000420 | Albuterol |
| D000111 | Acetylcysteine |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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|
| 0.9% saline + albuterol | Combination Product | The placebo comparator in this study is 0.9% normal saline (3 mL) and 2.5 mg albuterol inhalation solution (0.5 mL). |
|
|
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 2 Weeks |
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| BG001 |
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Forced Expiratory Volume in One Second (FEV1) Measurement | FEV1 in liters was assessed with participants in a seated position. FEV1 in liters was measured with a personal computer (PC) based spirometer until at least 3 acceptable and 2 repeatable maneuvers were captured. The highest maneuver was recorded. | Mean | Standard Deviation | Liters |
|
| Forced Expiratory Volume in One Second (FEV1) Measurement | 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. FEV1 percent predicted compares participants' FEV1 to the average for healthy individuals of similar age, height, gender, and ethnicity. | Mean | Standard Deviation | Percent Predicted |
|
| OG001 | Placebo | 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. |
|
|
| Primary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | Baseline and 2 Weeks |
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|
|
| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Mucus-plugged segments | 2 Weeks |
|
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|
| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | 2 Weeks |
|
|
|
| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | 2 Weeks |
|
|
|
| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Ratio | 2 Weeks |
|
|
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| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Parts per billion (ppb) | 2 Weeks |
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| Secondary | Absolute Eosinophil Count | Absolute eosinophil count is measured through blood tests. The absolute change in absolute eosinophil count at 2 weeks was calculated. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | cells x 10^9/L | 2 Weeks |
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| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | 2 Weeks |
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| Secondary | 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. | All participants who received at least one dose of each intervention and completed all study visits were included in the efficacy analysis. | Posted | Mean | Standard Deviation | Percent change | 2 Weeks |
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| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| EG001 | Placebo | 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. | 0 | 4 | 0 | 4 | 0 | 4 |
| Asthma exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000588 |
| Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D003545 | Cysteine |
| D000603 | Amino Acids, Sulfur |
| D013457 | Sulfur Compounds |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |