Asthma
Conditions
Brief summary
This study evaluates 20% n-acetylcystine (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 7-day treatment period and placebo in the next 7-day treatment period; and the other half will get placebo in the first 7-day treatment period and 20% NAC in the next 7-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 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.
Interventions
DRUGn-acetylcystine
NAC is a mucolytic drug.
DRUG0.9% saline
Normal saline is a placebo agent.
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Able to perform reproducible spirometry according to ATS criteria * Clinical history consistent with moderate to severe asthma for 1 year or greater. * Post-bronchodilator FEV1 \<90% of predicted * Prescription and daily use of inhaled corticosteroid (ICS) equivalent to 240mcg of beclomethasone or greater and a second asthma controller therapy. * CT mucus score \>3 (determined during the initial screening process, provided the prior two conditions are met) * Written informed consent obtained from participant and ability for participant to comply with the requirements of the study.
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. * History of intolerance to study medications. * Current use of carbamazepine * Angina which includes a treatment plan with PRN nitroglycerin or nitrites * Smoking of tobacco or other recreational inhalants in last year and/or \>10 pack-year smoking history * Current participation in an investigational drug trial Concurrent Medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Post-bronchodilator FEV1 (L) | 7 days | This is a measure of forced expiratory volume measured in one second, following the administration of 4 puffs of albuterol. This outcome will compare the change in post-bronchodilator FEV1 (L) both before and after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change CT Mucus Score | 7 days | The CT Mucus Score describes the number of segments of the lungs that are impacted by mucus. This outcome will compare the change in CT mucus score both at baseline and following each treatment period. |
Countries
United States
Participant flow
Pre-assignment details
9 subjects were consented to the study but only one remained eligible to continue to the treatment period after baseline eligibility testing and the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| 20% N-acetylcystine (NAC) NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 20% NAC delivered via nebulizer three times per day for seven days.
n-acetylcystine: NAC is a mucolytic drug. | 1 |
| 0.9% Saline Normal saline will be administered as the placebo agent via a nebulizer three times per day for seven days.
0.9% saline: Normal saline is a placebo agent. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | 20% N-acetylcystine (NAC) | 0.9% Saline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Change in Post-bronchodilator FEV1 (L)
This is a measure of forced expiratory volume measured in one second, following the administration of 4 puffs of albuterol. This outcome will compare the change in post-bronchodilator FEV1 (L) both before and after treatment.
Time frame: 7 days
Population: Only one subject was enrolled into the intervention, and after taking the first dose of NAC, they experienced excessive bronchospasm thus making them ineligible to continue and complete the study.
Secondary
Change CT Mucus Score
The CT Mucus Score describes the number of segments of the lungs that are impacted by mucus. This outcome will compare the change in CT mucus score both at baseline and following each treatment period.
Time frame: 7 days
Population: Only one subject was enrolled into the intervention, and after taking the first dose of NAC, they experienced excessive bronchospasm thus making them ineligible to continue and complete the study.