ENACT: The Effect of NAC on Lung Function and CT Mucus Score

Sponsor

University of California, San Francisco (Other)

Overall Status

Recruiting

CT.gov ID

NCT03822637

Collaborator

(none)

Enrollment

Location

Arms

36.3

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: n-acetylcystine + albuterol Drug: 0.9% saline + albuterol	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

The Effect of NAC on Lung Function and CT Mucus Score

Actual Study Start Date :

Feb 20, 2019

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 20% n-acetylcystine (NAC) 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 NAC is a mucolytic drug and Albuterol is a bronchodilator. Other Names: Mucomyst NAC n-acetylcystine
Placebo Comparator: 0.9% saline 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 Normal saline is a placebo agent and Albuterol is a bronchodilator. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: 20% n-acetylcystine (NAC)

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

NAC is a mucolytic drug and Albuterol is a bronchodilator.

Other Names:

Mucomyst

NAC

n-acetylcystine

Placebo Comparator: 0.9% saline

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

Normal saline is a placebo agent and Albuterol is a bronchodilator.

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Change in FEV1 [Through study completion, an average of 9 weeks]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Airway Clinical Research Center	San Francisco	California	United States	94143

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator: John Fahy, M.D, M.Sc., University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT03822637

Other Study ID Numbers:

18-26680

First Posted:

Jan 30, 2019

Last Update Posted:

Feb 1, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Acetylcysteine

Albuterol

N-monoacetylcystine

Study Results

No Results Posted as of Feb 1, 2022