Positive Airway Pressure + NAC for COPD
(TEAM Trial)
Recruiting in Palo Alto (17 mi)
Overseen byJohn Fahy, MD, MS
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of California, San Francisco
Must be taking: Inhaled corticosteroids, Biologic therapy
Disqualifiers: Pregnancy, URI, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
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 data supports the effectiveness of the treatment Positive Airway Pressure + NAC for COPD?
Research shows that salbutamol, a component of the treatment, can improve lung function in patients with pulmonary emphysema, a condition related to COPD, by increasing vital capacity (the maximum amount of air a person can expel from the lungs after a maximum inhalation). This suggests it may help improve breathing in COPD patients as well.
12345Is the combination of Positive Airway Pressure and NAC safe for humans?
The studies reviewed indicate that salbutamol (also known as albuterol or Ventolin) is generally safe and well-tolerated in humans when used for asthma and COPD. However, specific safety data for the combination of Positive Airway Pressure and N-acetylcysteine (NAC) for COPD is not directly available from these studies.
678910How does the drug Albuterol and NAC differ from other COPD treatments?
The combination of Albuterol (a bronchodilator) and NAC (N-acetylcysteine, which helps thin mucus) is unique because it not only helps open the airways but also improves mucus clearance, potentially offering dual benefits for COPD patients. This differs from other treatments that primarily focus on either bronchodilation or anti-inflammatory effects.
2581112Eligibility Criteria
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.
COPD Group: Written informed consent obtained from subject and ability for subject to comply with the requirements of the study
I have COPD and either have mucus plugging with no FEV1 limit or unknown plugging with FEV1<50%.
+12 more
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.
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: NAC via AeroEclipse-VersaPAPExperimental Treatment2 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 nebulizerActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCSF Airway Clinical Research CenterSan Francisco, CA
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Who Is Running the Clinical Trial?
University of California, San FranciscoLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
The effects of salbutamol aerosol on lung function in patients with pulmonary emphysema. [2019]The effects of inhaling 400 micrograms of salbutamol were compared with identical placebo inhaler in a double blind cross-over study of 20 patients with radiological evidence of pulmonary emphysema. There was a small but significant rise in the forced expiratory volume in one second (FEV1), but there was a much greater increase in vital capacity (VC), which was accompanied by a reduction in residual volume. Symptomatic improvement after salbutamol was reported by 14 of the patients and VC increased significantly in this group; there was no significant increase in VC in patients who did not prefer the active inhaler. There was no consistent change in the FEV1/VC ratio after salbutamol administration and this ratio is misleading as an indicator of bronchodilator responsiveness in patients with emphysema. Salbutamol is thus a valuable addition to treatment in patients with pulmonary emphysema and the response to treatment is best judged by measuring the improvement in VC.
Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. [2022]The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented. However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.
Evaluation of the Clinical Effectiveness of the Salmeterol/Fluticasone Fixed-Dose Combination Delivered via the Elpenhaler® Device in Greek Patients with Chronic Obstructive Pulmonary Disease and Comorbidities: The AEOLOS Study. [2021]Label="BACKGROUND" NlmCategory="BACKGROUND">Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory lung disease characterized by airflow limitation that is not completely reversible. The fixed-dose combination of salmeterol and fluticasone propionate (SFC) has been approved as a treatment for COPD patients with a history of recurrent exacerbations and significant symptoms despite regular bronchodilator therapy. In the present study, we evaluated the change in FEV1, mMRC dyspnea score and satisfaction in COPD patients with at least one comorbidity versus those without comorbidities treated with a fixed-dose SFC via the Elpenhaler® device for 12 months.
Effect of controlled-release salbutamol in predominantly non-reversible chronic airflow obstruction. [2019]We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to determine the efficacy of controlled release salbutamol (SCR) tablets in clinically stable patients with predominantly non-reversible chronic airflow obstruction (CAO). Patients received either 8 mg SCR or matching placebo tablets twice daily for 6 weeks. Fifty-eight patients (30 on SCR and 28 on placebo) completed the study. Outcome measurements included FEV1, FVC, 6-min walking distance, and patient assessment of efficacy recorded at the clinic visits and twice daily PEFR measurements plus daytime symptom score recorded in diary cards. The absolute change between baseline and 6-week measurements with SCR was compared to that with placebo. Favourable trends were observed with SCR for all variables tested except FVC. The only significant difference between SCR and placebo was in FEV1 where there was a small net change of 95 ml in favour of SCR. We conclude, therefore, that the effects of lung function of long-term bronchodilator therapy with SCR in patients with stable non-reversible CAO are slight, and are likely to be of limited clinical benefit.
A short-term comparison of fluticasone propionate/salmeterol with ipratropium bromide/albuterol for the treatment of COPD. [2019]This is the first comparison of two combination therapies, fluticasone propionate/salmeterol and ipratropium bromide/albuterol (salbutamol), for the treatment of patients with COPD.
Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group. [2018]This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation.
Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma. [2019]This study compares the safety and efficacy of HFA 134a salbutamol sulfate (Airomir in the 3M CFC-free system [3M Pharmaceuticals]) and CFC 11/12 salbutamol (Ventolin [Allen & Hanburys]) in a cumulative dose-response (1, 1, 2, 4, 8 inhalations at 30-min intervals) study in asthmatic patients.
Fluticasone propionate/salmeterol for the treatment of chronic-obstructive pulmonary disease. [2019]Chronic-obstructive pulmonary disease (COPD) is a global public health problem and its impact is increasing. Although only smoking cessation has been shown to alter the natural history of the disease, current treatment guidelines recommend the use of inhaled bronchodilators to decrease symptoms, improve lung function and quality of life and to prevent exacerbations. For a subset of patients with more severe disease, inhaled corticosteroids may also have a role in achieving these goals. Fluticasone propionate/salmeterol (Advair) or Seretide), GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator that is delivered by a dry-powder inhaler and was recently approved for use in COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and also appears to have important effects on the frequency of exacerbations and overall quality of life for some patients with COPD. Issues of patient selection as well as the pharmacology, efficacy and safety of the drug are discussed.
The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction. [2019]To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine.
Evaluation of the efficacy and safety of levalbuterol in subjects with COPD. [2019]The efficacy and safety of nebulized levalbuterol in adults with chronic obstructive pulmonary disease (COPD) was evaluated in this multicenter, randomized, double-blind, parallel design study. Randomized subjects (n = 209) received levalbuterol (LEV) 0.63 mg or 1.25 mg, racemic albuterol (RAC) 2.5 mg, or placebo (PBO) TID for 6 weeks. Serial spirometry was completed in-clinic after study drug alone (weeks 0, 2, and 6) or in combination with ipratropium bromide 0.5 mg (week 4). The primary endpoint was the averaged FEV1 AUC(0-8 hrs) over weeks 0, 2 and 6 compared with placebo. Other endpoints included rescue medication use, safety parameters, COPD exacerbations, and global evaluations. All active treatments demonstrated improvements in the percent change in FEV1 AUC(0-8 hrs) over the double-blind period and at each visit vs PBO (p
Chronic obstructive pulmonary disease: Useful medications for patients with recurrent symptoms. [2019]Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations. Severe disease may progress to chronic respiratory failure. We reviewed the literature on basic medications available for COPD, using the standard Prescrire methodology. There are few clinical data on treatment of mild COPD. Regular medication is not necessary for patients who do not have recurrent symptoms. Eliminating exposure to cigarette smoke and other irritants such as workplace irritants, is the only measure known to improve the outcome of COPD. Evaluation of inhaled short-acting beta-2 agonists is based mainly on short-term trials. These drugs have been shown to improve dyspnoea. Salmeterol and formoterol, two long-acting beta-2 agonists, have been extensively evaluated in symptomatic patients. Compared with no treatment, these drugs reduce breathlessness and acute exacerbations, preventing about two hospital admissions per 100 patients with moderate to severe COPD treated for 7 months. Indacaterol and olodateroldo not have a better harm-benefit balance. Inhaled beta-2 agonists occasionally provoke cardiovascular disorders. No excess mortality has been reported among the thousands of COPD patients included in clinical trials. There Is little evidence that ipratropium, an inhaled short-acting anti-muscarinic bronchodilator, improves COPD symptoms. A risk of Increased mortality among COPD patients treated with ipratroplum cannot be ruled out. Tiotroplum, an inhaled long-acting antimuscarinic bronchodilator, has been extensively evaluated In COPD. Tiotroplum has symptomatic efficacy in COPD, reducing dyspnoea and acute exacerbations. Tiotroplum had no tangible advantages over long-acting beta-2 agonists in seven randomised trials including more than 12 000 patients. Glycopyrronium and aclidinium, two other Inhaled long-acting antimuscarinics, do not appear to be more effective. Tiotroplum, like other inhaled anti-muscarinics, has antimuscarinic adverse effects including cardiac, visual and buccal disorders. Glycopyronium may carry a higher risk of serious cardiovascular effects. Combination of an antimuscarinic with an inhaled beta-2 agonist improves symptoms in 7% to 10% of patients. In patients with one or two COPD exacerbations per year, adding an Inhaled corticosterold (beclometa- sone, budesonide or fluticasone) to a long-acting beta-2 agonist prevents about 1 exacerbation during 3 to 4 years of treatment. Inhaled corticosteroids can cause pneumonia, candidiasis, dysphonia and adrenal Insufficiency. Fluticasone seems to have more adverse effects than other inhaled corticosterolds. Theophylline has uncertain efficacy on symptoms of COPD. This drug has a narrow therapeutic index and carries a risk of serious adverse effects. It should not be used in COPD. Long-term treatment with roflumilast or oral corticosteroids has an unfavourable harm-benefit balance in COPD. In practice, in 2016, the first measure in COPD is to eliminate exposure to the irritant, most often tobacco. Drugs used in COPD have only modest, mainly symptomatic efficacy. Treatment should be adapted to symptoms and the frequency of exacerbations: a short-acting beta-2 agonist should be tried first, then replaced by an inhaled long-acting bronchodilator, or possibly tiotropium, when its effect is too short-lived. An inhaled corticosteroid can be added if symptoms persist or exacerbations are frequent.
Effect of single inhalation of a salbutamol, ipratropium bromide and beclomethasone on mucociliary clearance in patients with chronic obstructive airway disease. [2016]Chronic obstructive airway disease (COAD) is associated with hyperplasia and hypertrophy of the mucus producing glands. The beneficial effect of inhaled drug may be due to improved mucociliary function. The present study was done to evaluate the effect of salbutamol, ipratropium bromide and beclomethasone dipropionate inhalation on mucociliary clearance in patients with COAD.