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

• ClinicalTrials.gov Identifier: NCT03822637
• Recruitment Status: Recruiting
• First Posted: January 30, 2019
• Last Update Posted: February 1, 2022
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: December 14, 2018
• First Posted Date: January 30, 2019
• Last Update Posted Date: February 1, 2022
• Actual Study Start Date: February 20, 2019
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2019)

Change in FEV1 [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effect of NAC on Lung Function and CT Mucus Score
• Official Title: The Effect of NAC on Lung Function and CT Mucus Score
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Asthma

Intervention

• Drug: n-acetylcystine + albuterol
  NAC is a mucolytic drug and Albuterol is a bronchodilator.
  Other Names:

  • Mucomyst
  • NAC
  • n-acetylcystine
• Drug: 0.9% saline + albuterol
  Normal saline is a placebo agent and Albuterol is a bronchodilator.
  Other Name: Normal saline

Study Arms

• 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.
  Intervention: Drug: n-acetylcystine + albuterol
• 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.
  Intervention: Drug: 0.9% saline + albuterol

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 28, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2022
• Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female between the ages of 18 and 80 years of age at Visit 1
2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
3. Able to perform reproducible spirometry according to American Thoracic Society (ATS) criteria
4. 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)
5. Clinical history of asthma per patient report or medical record
6. Pre-bronchodilator FEV1 > 35% predicted
7. Post-bronchodilator FEV1 > 40% but < 90% predicted
8. Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater
9. CT mucus score ≥ 5
10. Ability to tolerate study drug reflected by a post-treatment FEV1 ≥ 80% of pre- treatment, pre-bronchodilator FEV1

Exclusion Criteria:

1. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
2. 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
3. Smoking of tobacco or other recreational inhalants in last year and/or >10 pack-year smoking history
4. Adherence to study drug ≤ 70% after first treatment period
5. Current participation in an investigational drug trial
6. 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
7. Unwillingness to follow study procedures
8. History of allergy or intolerance to study drug
9. Any other criteria that places the subject at unnecessary risk according to the judgment of the Principal Investigator

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Xavier Orain, BS; 415-502-3472; xavier.orain@ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03822637
• Other Study ID Numbers: 18-26680
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of California, San Francisco
• Verification Date: January 2022