Positive Airway Pressure + NAC for COPD

(TEAM Trial)

Overseen By John Fahy, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must be taking: Inhaled corticosteroids, Biologic therapy

Disqualifiers: Pregnancy, URI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if positive airway pressure can help aerosolized N-Acetylcysteine (NAC) more effectively reach and clear mucus plugs in the lungs of individuals with asthma or Chronic Obstructive Pulmonary Disease (COPD). Researchers seek to compare the effectiveness of this method to using NAC without additional pressure. Participants will receive treatments using either a jet nebulizer or a special nebulizer called AeroEclipse-VersaPAP. Ideal candidates for this trial include individuals with asthma or COPD who frequently experience mucus buildup and regularly use inhalers or other asthma/COPD treatments. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to explore its potential benefits for a broader range of patients.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves treatments for asthma or COPD, it's possible that you may need to continue your existing inhaled corticosteroids or biologic therapy if you are in the asthma group.

What is the safety track record for these treatments?

Research has shown that nebulized N-acetylcysteine (NAC) is safe and effective for people with chronic obstructive pulmonary disease (COPD). One study found that patients used inhaled NAC for 12 weeks without serious side effects. This medicine thins mucus, making it easier to clear from the lungs.

In previous studies, patients demonstrated that inhaling NAC can reduce inflammation and improve lung function, which benefits those with COPD symptoms. The treatment is generally well-tolerated, with most people experiencing no major issues.

In this trial, NAC is administered with albuterol, a common medicine that helps open airways. Albuterol is known to be safe for most people. Both treatment methods in this trial (AeroEclipse-VersaPAP and jet nebulizer) use these medicines.

In summary, NAC and albuterol have a strong safety record for people with lung conditions like COPD. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for COPD, which often include inhaled corticosteroids and bronchodilators, this trial explores N-acetylcysteine (NAC) delivered in a unique way. Researchers are excited because NAC is administered alongside albuterol using two different systems: the AeroEclipse-VersaPAP and a standard jet nebulizer. The AeroEclipse-VersaPAP system is particularly intriguing because it may enhance the delivery and effectiveness of the medication compared to traditional methods. Additionally, NAC acts as a mucolytic agent, breaking down mucus and potentially improving lung function, which could offer a new approach to managing COPD symptoms beyond the typical focus on reducing inflammation and opening airways.

What evidence suggests that this trial's treatments could be effective for COPD?

Research has shown that N-Acetylcysteine (NAC) can improve the well-being and quality of life for people with Chronic Obstructive Pulmonary Disease (COPD). Studies have found that using NAC in a nebulizer effectively reduces mucus and enhances lung function. In this trial, participants will receive NAC through different delivery systems. One group will use the AeroEclipse-VersaPAP system, where positive airway pressure may help NAC reach and break down lung mucus more effectively. Another group will use a standard jet nebulizer. Patients who have used nebulized NAC experienced fewer symptoms and flare-ups. Overall, NAC is well-tolerated and useful in managing COPD symptoms. ^{3 5 6 7 8}

Who Is on the Research Team?

John Fahy, MD, MS

Principal Investigator

Professor of Medicine

Are You a Good Fit for This Trial?

Adults aged 18-85 with asthma or COPD, who are current/former smokers (COPD group) and have a history of using inhaled corticosteroids or biologic therapy for asthma. Participants must be able to perform spirometry tests and have a CT mucus score ≥3. Pregnant individuals or those with recent upper respiratory infections are excluded.

Inclusion Criteria

My asthma severity varies, but I can tolerate treatments without major lung function loss.

I have COPD and either have mucus plugging with no FEV1 limit or unknown plugging with FEV1<50%.

I can do a breathing test according to standard guidelines.

Exclusion Criteria

Currently pregnant

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

I have had an upper respiratory infection in the last 10 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive aerosolized NAC with or without positive inspiratory pressure over 5 treatment visits

4 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Albuterol
• Hillrom-Volara System
• NAC

Trial Overview The trial is testing if inhaling N-Acetylcysteine (NAC) combined with albuterol through positive pressure improves mucus clearance and lung function in patients compared to standard NAC inhalation without pressure. It's single-blind, meaning participants won't know which treatment they're getting.

How Is the Trial Designed?

Group I: NAC via AeroEclipse-VersaPAP Experimental Treatment 2 Interventions

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.

Group II: NAC via jet nebulizer Active Control 1 Intervention

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.

Albuterol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Albuterol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in European Union as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in Canada as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a 3-year study involving 6112 patients with moderate to severe COPD, inhaled salmeterol plus fluticasone propionate (SFC) significantly improved lung function (FEV1) and reduced exacerbation rates across all GOLD stages, with the most notable improvement in patients with moderate COPD (GOLD stage II).

SFC treatment was associated with a 33% reduction in mortality risk for patients with GOLD stage II COPD, indicating its potential as an effective treatment option, while the incidence of adverse events, including pneumonia, was similar across treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. Jenkins, CR., Jones, PW., Calverley, PM., et al.[2022]

In a study of 209 adults with COPD, nebulized levalbuterol (both 0.63 mg and 1.25 mg) showed significant improvements in lung function (FEV1) compared to placebo, indicating its efficacy as a bronchodilator.

Levalbuterol was generally well tolerated, with a lower rate of rescue medication use compared to racemic albuterol, and fewer withdrawals due to COPD exacerbations, suggesting it may offer better clinical control for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy and safety of levalbuterol in subjects with COPD. Donohue, JF., Parsey, MV., Andrews, C., et al.[2019]

In a study of 20 patients with pulmonary emphysema, inhaling 400 micrograms of salbutamol led to a significant increase in vital capacity (VC) and a reduction in residual volume, indicating improved lung function.

14 out of 20 patients reported symptomatic improvement after using salbutamol, suggesting it is an effective treatment option for enhancing respiratory function in emphysema, with VC being a better measure of response than the FEV1/VC ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of salbutamol aerosol on lung function in patients with pulmonary emphysema. Bellamy, D., Hutchison, DC.[2019]

In a 12-month study involving 1016 COPD patients, treatment with the fixed-dose combination of salmeterol and fluticasone propionate (SFC) significantly improved lung function (FEV1) and dyspnea scores, regardless of the presence of comorbidities.

Patients without comorbidities experienced greater improvements in lung function compared to those with comorbidities, but both groups showed statistically significant benefits, indicating the efficacy of SFC in managing COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Clinical Effectiveness of the Salmeterol/Fluticasone Fixed-Dose Combination Delivered via the Elpenhaler&#174; Device in Greek Patients with Chronic Obstructive Pulmonary Disease and Comorbidities: The AEOLOS Study. Steiropoulos, P., Tryfon, S., Kyriakopoulos, C., et al.[2021]

Fluticasone propionate/salmeterol (Advair) is an effective treatment for chronic obstructive pulmonary disease (COPD), improving lung function, reducing symptoms, and enhancing quality of life for some patients.

This combination inhaler not only acts as a potent bronchodilator but also helps decrease the frequency of exacerbations in patients with more severe COPD, although careful patient selection is important for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone propionate/salmeterol for the treatment of chronic-obstructive pulmonary disease. Dransfield, MT., Bailey, WC.[2019]

Eliminating exposure to irritants like tobacco smoke is the most effective measure for improving outcomes in COPD, as regular medication is not necessary for patients without recurrent symptoms.

Long-acting beta-2 agonists, such as salmeterol and formoterol, significantly reduce breathlessness and acute exacerbations in moderate to severe COPD, preventing about two hospital admissions per 100 patients treated for 7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic obstructive pulmonary disease: Useful medications for patients with recurrent symptoms. [2019]

In a study involving 24 asthmatic patients, both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol showed equivalent improvements in lung function (FEV1 and FVC) after inhalation, indicating similar efficacy.

The safety profiles of both medications were comparable, with no significant differences in heart rate, blood pressure, or adverse events, suggesting that HFA 134a salbutamol sulfate is a safe alternative to CFC 11/12 salbutamol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma. Kleerup, EC., Tashkin, DP., Cline, AC., et al.[2019]

Inhalation of salbutamol (100 microg) significantly protects against bronchoconstriction induced by methacholine in patients with moderate asthma, regardless of the inhalation device used (pMDI, pMDI + spacer, or Autohaler).

While there was a slight trend suggesting that using a pMDI with a spacer may enhance the protective effect of salbutamol, the differences among the inhalation techniques were not statistically significant, confirming the drug's efficacy across various methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction. Giannini, D., Di Franco, A., Bacci, E., et al.[2019]

In a study involving 10 patients with chronic obstructive airway disease (COAD), inhaled salbutamol, ipratropium bromide, and beclomethasone dipropionate did not significantly improve mucociliary clearance compared to a placebo.

Although two patients showed some improvement with salbutamol, overall, the results indicated that a single dose of these inhaled medications does not appreciably enhance mucociliary function in COAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of single inhalation of a salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic obstructive airway disease. Guleria, R., Singh, TR., Sinha, S., et al.[2016]

In a study involving 423 patients with mild to moderate asthma, both CFC and HFA formulations of salbutamol were found to be equally effective in improving lung function and managing asthma symptoms over a 4-week period.

Both inhaler formulations were well tolerated by patients, indicating that the HFA 134a pMDI is a safe alternative to the CFC pressurized metered dose inhaler for delivering salbutamol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group. Baumgarten, CR., Dorow, P., Weber, HH., et al.[2018]

In a study involving 365 patients with COPD over 8 weeks, fluticasone propionate/salmeterol was found to be more effective than ipratropium bromide/albuterol in improving lung function and reducing symptoms, including morning pre-dose FEV(1) and nighttime awakenings.

Both treatments had similar safety profiles, but fluticasone propionate/salmeterol was associated with a higher incidence of oral candidiasis, indicating a potential side effect to monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A short-term comparison of fluticasone propionate/salmeterol with ipratropium bromide/albuterol for the treatment of COPD. Donohue, JF., Kalberg, C., Emmett, A., et al.[2019]

In a study involving 58 patients with chronic airflow obstruction, controlled release salbutamol (SCR) showed a small but significant improvement in lung function measured by FEV1, with a net change of 95 ml compared to placebo after 6 weeks.

Despite some favorable trends in other measurements, the overall benefits of SCR in improving lung function were minimal, suggesting limited clinical significance for patients with stable non-reversible chronic airflow obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of controlled-release salbutamol in predominantly non-reversible chronic airflow obstruction. Mohammed, AF., Anderson, K., Matusiewicz, SP., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38555190/

N-acetylcysteine Treatment in Chronic Obstructive ... These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD.

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06152653

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 ...

3. archbronconeumol.org archbronconeumol.org/es-n-acetylcysteine-treatment-in-chronic-obstructive-articulo-S0300289624000693

N-acetylcysteine Treatment in Chronic Obstructive ... These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10026096/

The efficacy of N-acetylcysteine in chronic obstructive ... We hypothesize that chronic obstructive pulmonary disease patients receiving regular oral NAC therapy do not achieve improved clinical outcomes.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01599884

N-Acetylcysteine for Patients With COPD and ... It is postulated that substantially higher doses of NAC will be well-tolerated and will provide better symptom control while also decreasing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06152653

The Effects of Positive Airway Pressure on the Mucolytic ... The goal of this clinical trial is to determine if positive pressure during inspiration will improve penetration of aerosolized N-Acetylcysteine (NAC) into ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39223526/

The effect of nebulized N-acetylcysteine on the phlegm ... In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks. Keywords: Chronic bronchitis; Chronic obstructive pulmonary ...

8. bmcpulmmed.biomedcentral.com bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-024-03243-y

The effect of nebulized N-acetylcysteine on the phlegm of ... N-acetylcysteine (NAC) is a commonly prescribed oral medication in COPD patients. Previous studies have demonstrated that NAC effectively reduces exacerbation ...