Clinical Trial of NAC in Asthma

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

Official Title
-----------------
Clinical Trial of NAC in Asthma

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

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


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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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 delivered via nebulizer three times per day for seven days. | Drug: n-acetylcystine<br>* NAC is a mucolytic drug.<br>* Other names: acetylcystine;|
| Placebo Comparator: 0.9% saline<br>Normal saline will be administered as the placebo agent via a nebulizer three times per day for seven days. | Drug: 0.9% saline<br>* Normal saline is a placebo agent.<br>* Other names: Normal saline;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 7 days |