ICON: Inpatient Clinical Trial of NAC
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the beneficial effect of n-acetylcysteine (NAC), an inhaled medication that breaks down mucus, on lung function. NAC is a medication approved by the US Food and Drug Administration (FDA) for the treatment of chronic diseases of the respiratory system, including asthma. With CT lung imaging, the investigators seek to identify a subgroup of patients with asthma with a 'mucus' profile. This is a single-arm study which means all participants will receive the same treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 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 single-arm study of participants 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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: N-acetylcysteine This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. |
Drug: N-acetylcysteine
Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart.
|
Outcome Measures
Primary Outcome Measures
- Forced Expiratory Volume in One Second (FEV1) Measurement [end of the one week treatment period]
Post-treatment FEV1 is reported. FEV1 is measured via spirometry.
Secondary Outcome Measures
- Computed Tomography (CT) Scan Mucus Score [From the start of the one week treatment period to the three month follow-up]
Post-treatment CT mucus scores will be compared to pre-treatment CT mucus score
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 ATS criteria
-
Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥ 12% or hyperreactivity to methacholine reflected by a methacholine PC20 ≤ 16 mg/mL)
-
Clinical history of asthma per patient report or medical record
-
Pre-bronchodilator FEV1 > 35% predicted
-
Post-bronchodilator FEV1 > 40% but < 90% predicted
-
Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater
-
CT mucus score > 3
Exclusion Criteria:
-
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
-
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
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco | San Francisco | California | United States | 94143 |
Sponsors and Collaborators
- University of California, San Francisco
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: John Fahy, M.D, M.Sc., University of California, San Francisco
Study Documents (Full-Text)
More Information
Publications
- DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13:27-33.
- Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9.
- 17-24231
- P01HL128191
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | N-acetylcysteine |
|---|---|
| Arm/Group Description | This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. N-acetylcysteine: Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart. |
| Period Title: Overall Study | |
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | N-acetylcysteine |
|---|---|
| Arm/Group Description | This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. N-acetylcysteine: Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart. |
| Overall Participants | 1 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
1
100%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
1
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
0
0%
|
| More than one race |
1
100%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (Count of Participants) | |
| United States |
1
100%
|
| Forced Expiratory Volume in One Second (FEV1) Measurement (liters) [Number] | |
| Number [liters] |
.85
|
| Mean Number of Mucus Plugs (number of mucus plugs) [Mean (Full Range) ] | |
| Mean (Full Range) [number of mucus plugs] |
11
|
Outcome Measures
| Title | Forced Expiratory Volume in One Second (FEV1) Measurement |
|---|---|
| Description | Post-treatment FEV1 is reported. FEV1 is measured via spirometry. |
| Time Frame | end of the one week treatment period |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | N-acetylcysteine |
|---|---|
| Arm/Group Description | This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. N-acetylcysteine: Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart. |
| Measure Participants | 1 |
| Number [liters] |
0.86
|
| Title | Computed Tomography (CT) Scan Mucus Score |
|---|---|
| Description | Post-treatment CT mucus scores will be compared to pre-treatment CT mucus score |
| Time Frame | From the start of the one week treatment period to the three month follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| The researchers were unable to obtain a post-treatment CT scan for the enrolled subject and therefore have nothing to report for this outcome measure. |
| Arm/Group Title | N-acetylcysteine |
|---|---|
| Arm/Group Description | This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. N-acetylcysteine: Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 3 months | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events will be monitored by the Clinical PIs (Drs. Fahy, Woodruff and Lazarus) in real-time. Safety and tolerability data will be summarized quarterly. Adverse events will be tabulated and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug. All AEs will be reviewed quarterly. | |
| Arm/Group Title | N-acetylcysteine | |
| Arm/Group Description | This study will look at the effects of a medication, called n-acetylcysteine or NAC, on lung function. NAC is already approved for use in people with chronic airway conditions, including asthma. However, it is not known who this medication works best in. We believe this medication will likely have the most benefit in people with asthma that have mucus in their airways or "mucus plugging." Initial study procedures will include lung function measurements, a low dose CT scan, a blood draw, and a sputum induction. The CT lung imaging will identify asthmatics with mucus plugs. N-acetylcysteine: Research participants that meet the study inclusion criteria will be admitted to a medical-surgical ward in Moffitt-Long Hospital (UCSF Medical Center) for 6 days and 5 nights and treated with an inhaled mixture of NAC and albuterol four times per day spaced at 4 to 6 hours apart. | |
All Cause Mortality |
||
| N-acetylcysteine | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/1 (0%) | |
Serious Adverse Events |
||
| N-acetylcysteine | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| Cardiac disorders | ||
| Angina | 1/1 (100%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| N-acetylcysteine | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/1 (100%) | |
| General disorders | ||
| Headache | 1/1 (100%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ariana Lowman |
|---|---|
| Organization | UCSF Airway Clinical Research Center |
| Phone | 14155141539 |
| ariana.baum@ucsf.edu |
- 17-24231
- P01HL128191