The Effect of NAC on Lung Function and CT Mucus Score

Study Overview
=================
Brief 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 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.

Official Title
-----------------
The Effect of NAC on Lung Function and CT Mucus Score

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: n-acetylcystine + albuterol
* Drug: 0.9% saline + albuterol


Participation Criteria
=================
Eligibility 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 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 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 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 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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20% n-acetylcystine (NAC)<br>NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 20% NAC coadministered with albuterol and delivered via nebulizer three times per day for fourteen days. | Drug: n-acetylcystine + albuterol<br>* NAC is a mucolytic drug and Albuterol is a bronchodilator.<br>* Other names: n-acetylcystine;|
| Placebo Comparator: 0.9% saline<br>Normal saline will be coadministered with albuterol as the placebo agent via a nebulizer three times per day for fourteen days. | Drug: 0.9% saline + albuterol<br>* Normal saline is a placebo agent and Albuterol is a bronchodilator.<br>* Other names: Normal saline;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FEV1 | The primary outcome is the % change in FEV1 from the start to the end of each two-week treatment period (either placebo or 20% NAC). | Through study completion, an average of 9 weeks |