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

Asthma Clinical Trial

— TEAM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06152653
• Other study ID #: 23-39679
• Secondary ID: 2R01HL080414-13A
• Status: Recruiting
• Phase: Phase 4
• Start date: July 1, 2024
• Est. completion date: November 21, 2027

Study information

• Verified date: March 2024
• Source: University of California, San Francisco
• Contact: Xavier Orain, BS
• Phone: 415-502-3472
• Email: xavier.orain[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: November 21, 2027
• Est. primary completion date: November 21, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• COPD

Intervention

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

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

Locations

Country	Name	City	State
United States	UCSF Airway Clinical Research Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View 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. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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