Clinical trial NCT02605824: Clinical Trial of NAC in Asthma
Official title: Clinical Trial of NAC in Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2015-11-16
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Post-bronchodilator FEV1 (L)
timeFrame: 7 days
Secondary outcomes:
measure: Change CT Mucus Score
timeFrame: 7 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Airway Clinical Research Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: John V Fahy, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.