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

NCT06152653 | Recruiting Phase 4 DMC FDA Drug FDA Device

• 2 other identifiers: 23-396792R01HL080414-13A1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma; COPD

Keywords

Asthma; COPD; Mucolytic; Mucus Plug; Positive Pressure; NAC

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

NAC via jet nebulizer

ACTIVE COMPARATOR

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 via AeroEclipse-VersaPAP

EXPERIMENTAL

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; Device: AeroEclipse-VersaPAP System

Interventions

n-acetylcystine (NAC)+ albuterol DRUG

NAC is a mucolytic drug and Albuterol is a bronchodilator.

Also known as: Mucomyst, NAC

NAC via AeroEclipse-VersaPAP; NAC via jet nebulizer

AeroEclipse-VersaPAP System DEVICE

The AeroEclipse-VersaPAP System combine continuous positive inspiratory pressure and nebulizer in one system.

Also known as: VersaPAP System

NAC via AeroEclipse-VersaPAP

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Asthma Group:
• Male or female between the ages of 18 to 85 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
• Clinical history of asthma per patient report or medical record
• Asthma requiring treatment with inhaled corticosteroids (ICS) or biologic therapy for 3 months or greater
• Computed Tomography (CT) mucus score ≥ 3 (done as part of screening)
• 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.
• For participants with known mucus plugging on CT: no limit on FEV1;
• For participants with unknown mucus plugging: FEV1\<70% predicted
• COPD Group:
• Males or females between the ages 18 to 85 at the time of visit 1.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• History of COPD per patient report or medical record and confirmed by an FEV1/FVC ratio of under 70%.
• Current or former smoker with a history of at least 10 pack-years of smoking.

You may not qualify if:

• 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.
• Currently pregnant
• URI in past 10 days

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UCSF Airway Clinical Research Center

San Francisco, California, 94143, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 12867239 BACKGROUND

• 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.

  PMID: 13818688 BACKGROUND

• 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.

  PMID: 26565159 BACKGROUND

• 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.

  PMID: 35104436 BACKGROUND

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive

Interventions

N-monoacetylcystine; Acetylcysteine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• John Fahy, MD, MS

  Professor of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade Vi, BS

CONTACT

415-476-1783; jade.vi@ucsf.edu

John Fahy, MD, MS

CONTACT

415-476-9940; john.fahy@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 1, 2023
• Study Start: April 9, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)