The Effects of Positive Airway Pressure on the Mucolytic Effects of NAC (TEAM) (TEAM)

The Effects of Positive Airway Pressure on the Mucolytic Effects of NAC

The goal of this clinical trial is to determine if positive pressure during inspiration will improve penetration of aerosolized N-Acetylcysteine (NAC) into airway mucus plugs in the lungs of patients with asthma or Chronic Obstructive Pulmonary Disease (COPD).

The main questions it aims to answer are:

• Does delivery of aerosolized NAC with positive inspiratory pressure have a greater effect on mucus plug burden in the lungs than delivery of NAC without positive pressure.
• Does delivery of aerosolized NAC with positive inspiratory pressure have a greater effect on lung function than delivery of NAC without positive pressure.

Participants will be assigned (in a single blind design) to the NAC via jet nebulizer group or the NAC via AeroEclipse-VersaPAP nebulizer group. Participants will each complete 5 treatment visits over the course of 30 days. Each treatment visit will consist of two treatments of a 10% NAC (3 mL) and 2.5 mg albuterol (0.5mL) inhalation solution separated by 4 hours, via the nebulization method specific to their group.

Study Overview

• Status: Recruiting
• Conditions: Asthma; COPD
• Intervention / Treatment: Drug: n-acetylcystine (NAC)+ albuterol; Device: AeroEclipse-VersaPAP System

Detailed Description

The optimal method for delivering aerosolized N-acetyl cysteine (NAC, Mucomyst) to the airways for the purpose of lysing mucus plugs is not established. The challenge is to ensure that the NAC aerosol penetrates the mucus plug to lyse it. We hypothesize that increasing the inspiratory pressure during aerosol inhalation will improve mixing of NAC with plugs and increase the chance of lysis within the time that the NAC liquid medication "dwells" in the plugged airway segment. Usual nebulizer systems that generate aerosols for inhalation do not allow for application of pressure during inspiration, but the VersaPAP system (from Monaghan Medical Corporation) has this capability. Specifically, the VersaPAP system combines continuous positive pressure during inspiration while the patient inhales aerosol medication, and the pressure will generate viscous fingers in the mucus plugs to aid lysis.

Recent published work from the Fahy lab has revealed that airway mucus plugs can be identified on low dose CT scans of the lungs and quantified using a bronchopulmonary segment based system to generate a measure that quantifies the mucus plug burden in the lung. This CT based mucus plug scoring system provides a predictive and monitoring biomarker for mucus plug pathology in the lungs of patients with asthma and COPD.

This is a single-blind phase 4 clinical trial designed to help determine the optimal method of delivery of aerosolized NAC to patients with mucus-associated lung disease (asthma and COPD). Subjects will be screened for evidence of mucus in their lungs as determined by CT imaging. Eligible participants will then be assigned to the NAC via jet nebulizer group or the NAC via AeroEclipse-VersaPAP nebulizer group and complete 5 treatment visits over the course of 30 days. Each treatment visit will consist of two treatments of a 10% NAC (3 mL) and 2.5 mg albuterol (0.5mL) inhalation solution separated by 4 hours, via the nebulization method specific to their group.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: John Fahy, MD, MS; Phone Number: 415-476-9940; Email: john.fahy@ucsf.edu
• Study Contact Backup: Name: Jade Vi, BS; Phone Number: 415-476-1783; Email: jade.vi@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Airway Clinical Research Center
      • Contact: John Fahy, MD, MS; Phone Number: 415-476-9940; Email: john.fahy@ucsf.edu
      • Principal Investigator: John Fahy, MD, MS
      • Contact: Jade Vi, BS; Phone Number: 415-476-1783; Email: jade.vi@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Asthma Group:

1. Male or female between the ages of 18 to 85 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. Clinical history of asthma per patient report or medical record
5. Asthma requiring treatment with inhaled corticosteroids (ICS) or biologic therapy for 3 months or greater
6. Computed Tomography (CT) mucus score ≥ 3 (done as part of screening)
7. There is no lower threshold on Forced Expiratory Volume in the first second (FEV1), which means the study will attempt to enroll all patients regardless of asthma severity. However, eligible participants will need to demonstrate ability to tolerate study treatment reflected by a post-treatment FEV1 ≥ 80% of pre- treatment, pre-bronchodilator FEV1. Participants who have a >20% drop in FEV1 after receiving any study treatment will be excluded from the study.
8. For participants with known mucus plugging on CT: no limit on FEV1;

For participants with unknown mucus plugging: FEV1<70% predicted

COPD Group:

1. Males or females between the ages 18 to 85 at the time of visit 1.
2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
3. History of COPD per patient report or medical record and confirmed by an FEV1/FVC ratio of under 70%.
4. Current or former smoker with a history of at least 10 pack-years of smoking.
5. CT mucus score ≥ 3
6. There is no lower threshold on FEV1, which means the study will attempt to enroll all patients regardless of COPD severity. However, eligible participants will need to demonstrate ability to tolerate study treatment reflected by a post-treatment FEV1 ≥ 80% of pre- treatment, pre-bronchodilator FEV1. Participants who have a >20% drop in FEV1 after receiving any study treatment will be excluded from the study.
7. For participants with known mucus plugging on CT: no limit on FEV1; For participants with unknown mucus plugging: FEV1<50% predicted

Exclusion Criteria:

1. A history of medical disease, which in the opinion of the investigator may put the subject at extra risk from study-related procedures or because the disease may influence the results of the study.
2. Currently pregnant
3. URI in past 10 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NAC via jet nebulizer; NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 10% NAC coadministered with albuterol and delivered via standard jet nebulizer. Participants will each complete 5 treatment visits over the course of 30 days. Each treatment visit will consist of two treatments separated by 4 hours.	Drug: n-acetylcystine (NAC)+ albuterol; NAC is a mucolytic drug and Albuterol is a bronchodilator.; Other Names: NAC; Mucomyst
Experimental: NAC via AeroEclipse-VersaPAP; NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 10% NAC coadministered with albuterol and delivered via the AeroEclipse-VersaPAP system. Participants will each complete 5 treatment visits over the course of 30 days. Each treatment visit will consist of two treatments separated by 4 hours.	Drug: n-acetylcystine (NAC)+ albuterol; NAC is a mucolytic drug and Albuterol is a bronchodilator.; Other Names: NAC; Mucomyst; Device: AeroEclipse-VersaPAP System; The AeroEclipse-VersaPAP System combine continuous positive inspiratory pressure and nebulizer in one system.; Other Names: VersaPAP System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mucus plug score	The primary outcome is the % change in mucus plug score from 1 week before treatment to 1 week post treatment.	1 week before treatment to 1 week post treatment, an average of 6 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: John Fahy, MD, MS, Professor of Medicine

Publications and helpful links

General 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.
• Chui JY, de Anna P, Juanes R. Interface evolution during radial miscible viscous fingering. Phys Rev E Stat Nonlin Soft Matter Phys. 2015 Oct;92(4):041003. doi: 10.1103/PhysRevE.92.041003. Epub 2015 Oct 28.
• Tang M, Elicker BM, Henry T, Gierada DS, Schiebler ML, Huang BK, Peters MC, Castro M, Hoffman EA, Fain SB, Ash SY, Choi J, Hall C, Phillips BR, Mauger DT, Denlinger LC, Jarjour NN, Israel E, Phipatanakul W, Levy BD, Wenzel SE, Bleecker ER, Woodruff PG, Fahy JV, Dunican EM. Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time. Am J Respir Crit Care Med. 2022 May 1;205(9):1036-1045. doi: 10.1164/rccm.202110-2265OC.

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 22, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Asthma; COPD; NAC; Mucolytic; Mucus Plug; Positive Pressure
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Asthma; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Reproductive Control Agents; Antiviral Agents; Neurotransmitter Agents; Antioxidants; Protective Agents; Adrenergic Agonists; Adrenergic Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antidotes; Anti-Asthmatic Agents; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Acetylcysteine; N-monoacetylcystine; Albuterol
• Other Study ID Numbers: 23-39679; 2R01HL080414-13A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No