Clinical Trial of NAC in Asthma (CONA)
Primary Purpose
Asthma
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
n-acetylcystine
0.9% saline
Sponsored by
About this trial
This is an interventional treatment trial for Asthma
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
Sites / Locations
- UCSF Airway Clinical Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
20% n-acetylcystine (NAC)
0.9% saline
Arm Description
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.
Normal saline will be administered as the placebo agent via a nebulizer three times per day for seven days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT02605824
First Posted
November 12, 2015
Last Updated
July 29, 2019
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT02605824
Brief Title
Clinical Trial of NAC in Asthma
Acronym
CONA
Official Title
Clinical Trial of NAC in Asthma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
The study was closed after we determined that this albuterol/NAC regimen may be associated with excessive bronchoconstriction.
Study Start Date
March 2016 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
20% n-acetylcystine (NAC)
Arm Type
Experimental
Arm Description
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.
Arm Title
0.9% saline
Arm Type
Placebo Comparator
Arm Description
Normal saline will be administered as the placebo agent via a nebulizer three times per day for seven days.
Intervention Type
Drug
Intervention Name(s)
n-acetylcystine
Other Intervention Name(s)
Mucomyst, NAC, acetylcystine
Intervention Description
NAC is a mucolytic drug.
Intervention Type
Drug
Intervention Name(s)
0.9% saline
Other Intervention Name(s)
Normal saline
Intervention Description
Normal saline is a placebo agent.
Primary Outcome Measure Information:
Title
Change in Post-bronchodilator FEV1 (L)
Description
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
Secondary Outcome Measure Information:
Title
Change CT Mucus Score
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John V Fahy, MD, MSc
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF Airway Clinical Research Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
12867239
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.
Results Reference
background
PubMed Identifier
13818688
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.
Results Reference
background
Links:
URL
http://acrc.ucsf.edu
Description
Study Center Website
Learn more about this trial
Clinical Trial of NAC in Asthma
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