ACRC Clinical Trials

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Though some medicines can help relieve symptoms of COPD, no treatment other than quitting smoking has been shown to slow the progression of the disease. 

Losartan is a drug that may be useful in slowing the progression of COPD. This medication is currently used to treat high blood pressure and heart failure, and data from clinical trials suggest that it may be useful in slowing the progression of COPD, particularly emphysema. Losartan has not been approved to treat COPD. The purpose of this study was to see if losartan helps to slow the progression of COPD-related emphysema in the lungs. 

The primary outcome of LEEP was to perform a placebo controlled trial of losartan for people with mild to severe COPD in ALA-ACRC centers to determine if it changes the rate of progression of emphysema, as measured by quantitative changes in high-resolution computed tomography (HRCT) of the lungs. 

Follow-up on all participants was completed in 2021. Investigators are currently preparing a manuscript describing the results of the trial. We will share the results of the trial once they have been published. 

Some LEEP participants have participated in an ancillary study to LEEP aimed at understanding the impact of the COVID-19 pandemic on people with COPD. Preliminary results of the study were presented at the American Thoracic Society conference in April 2021 (LaBedz, S. (2021, May 14-19). Anxiety, depressive symptoms, and attitudes about COVID-19 in patients with chronic obstructive pulmonary disease [Conference presentation]. ATS 2021 Conference, online). A manuscript will be submitted with complete results from Phase 1 of the study. An important finding from that study is the resilience of participants while coping with the restrictions and stress caused by the pandemic. 

Co-funded by the National Heart, Lung and Blood Institute

Co-funded by the National Heart, Lung and Blood Institute

Do mobile and internet technology make clinical trials more convenient and cost effective?

Funded by the American Lung Association 

Examines the relationship between anxiety, health status and prognosis, to inform appropriate treatment strategies.

Funded by the American Lung Association

Evaluates measurements of cough symptoms and the impact of cough on quality of life for people with chronic cough.

Funded by the American Lung Association

ZICO will look at how well tolerated and how safe taking zinc to treat chronic cough is. Results of COCO and ZICO will be used to develop a full-scale trial to test treating chronic cough with zinc acetate.

The ACRC network is studying whether having regular video calls with a pharmacist using a smart phone or computer will help adolescents and young adults with asthma to regularly take their prescribed inhaled medications and have fewer asthma symptoms. 

Obesity is a risk factor for the development of asthma and people with obesity often have poorly controlled asthma and do not respond as well to conventional controller therapy as lean asthmatics. Obesity particularly affects minority populations. 

Roflumilast is a drug that might be particularly useful for the treatment of asthma in obesity and is currently used in the treatment of chronic obstructive pulmonary disease.  Data in clinical trials support efficacy of this medication in the treatment of asthma, though it has never been approved for treating asthma in the general population, likely because of concern about side-effects; but these “side-effects” may actually contribute to efficacy in the treatment of asthma in obesity.  

The primary objective of this trial was to perform a small placebo controlled trial of roflumilast for the treatment of poorly controlled asthma in people with obesity in select centers of the ALA-ACRC to determine the effectiveness and tolerability of our intervention in obese asthma. We will share the results of the trial after publication. Thank you to all our participants for their time!

Weight loss might improve asthma control in people with obesity.  However, people with asthma might have particular challenges losing weight and the amount of weight loss needed to improve asthma control is not clear. The purpose of this study was to pilot test whether an online weight loss intervention could achieve an effect size suggested by the FDA as a criterion for evaluating weight loss interventions (>=5% weight loss in at least 35% of participants)  and to estimate the impact of this amount of weight loss on asthma control. We will share the results of the study after publication. Thank you to all our participants for their time!

Poorly controlled asthma is common in people with obesity, and standard treatments for asthma don’t work as well in people with obesity. The purpose of this study was to understand factors that might make it difficult to treat asthma in people with obesity in order to develop more effective treatments. We enrolled 102 participants with an average (median) BMI of 37. The majority were African American women. Most had very poorly controlled asthma and were quite sedentary. They reported significant impairments in health related to physical functioning, and also had mild to moderate depressive symptoms. Interventions targeted at poorly controlled asthma associated with obesity in the United States need to address factors complicating health in underserved communities, such as increasing opportunities for physical activity, while also managing activity limitations related to the combination of asthma and obesity. Thank you to all our participants for their time! You can read more about the results here: https://onlinelibrary.wiley.com/doi/full/10.1002/osp4.533

Published by: The American Lung Association

Study: The REACH study investigated airway obstruction in 582 children. Pulmonary diagnoses included asthma (93%), prior significant pneumonia (28%), and bronchiectasis (5%). 65% reported allergic rhinitis, and 11% chronic sinusitis. Subjects without a history of asthma had significantly lower post-BD FEV1% predicted (p = 0.008). Subjects without allergic rhinitis had lower post-BD FEV1% predicted (p = 0.003). Children with allergic rhinitis, males, obesity and Black race had better pulmonary function post-BD. There was lower pulmonary function in children after age 11 years without a history of allergic rhinitis, as compared to those with a history of allergic rhinitis. The most prevalent diagnosis in children with BD-resistant airflow limitation is asthma. Allergic rhinitis and premature birth are common co-morbidities. Children without a history of asthma, as well as those with asthma but no allergic rhinitis, had lower pulmonary function. Children with BD-resistant airflow limitation may represent a sub-group of children with persistent obstruction and high risk for life-long airway disease.

Published by: The American Lung Association

Study: What is the best way to reduce treatment in well-controlled asthmatic patients?

The study was funded by the American Lung Association (ACRC Network) and an unrestricted grant from GlaxoSmithKline

Published by: The American Lung Association

Study: This study enrolled adults with asthma who smoked weeks. The statistical properties, validity, and responsiveness of the Asthma Control Test (ACT) were evaluated in these patients. Physician global assessment of asthma was the "gold standard." The study found that ACT questionnaire was reliable and discriminated between levels of asthma control in smoking asthmatics with similar sensitivity and specificity as nonsmoking asthmatics, which confirms its value as a tool for the management of asthma in this prevalent but understudied subgroup of subjects.

The study was co-funded by the National Heart, Lung and Blood Institute

Published by: The Annals of the American Thoracic Society, August 2018

Study: Although national and international guidelines recommend reduction of asthma controller therapy or "step-down" therapy in patients with well-controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. A factor that may impact on treatment failure is exposure to secondhand smoke. The present findings can help clinicians identify adults and adolescents with asthma who are more likely to develop treatment failure and exacerbations and who may therefore require closer monitoring during asthma step-down treatment. Adults and Adolescents with reduced pulmonary function, a history of exacerbations and early onset disease may require closer observation during guidance-based step-down therapy.

The study was funded by the American Lung Association (ACRC Network) and an unrestricted grant from GlaxoSmithKline

Published by: The Annals of the American Thoracic Society, August 2018

Study: Although national and international guidelines recommend reduction of asthma controller therapy or "step-down" therapy in patients with well-controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. A factor that may impact on treatment failure is exposure to secondhand smoke. The present findings can help clinicians identify adults and adolescents with asthma who are more likely to develop treatment failure and exacerbations and who may therefore require closer monitoring during asthma step-down treatment. Adults and Adolescents with reduced pulmonary function, a history of exacerbations and early onset disease may require closer observation during guidance-based step-down therapy.

The study was funded by the American Lung Association (ACRC Network) and an unrestricted grant from GlaxoSmithKline

Published by: Journal of Asthma, May 2018

Study: The purpose of this study was to identify factors associated with depressive symptoms in a large (599 subjects) diverse group of patients with poorly controlled asthma. The study found that subjects with depressive symptoms have significantly less knowledge of their asthma, and poorer quality of life compared to those without depressive symptoms. These findings are not dependent on either age or gender. The authors recommend that a larger and more diverse study evaluating the impact of depression on asthma control  would be important.

The study was funded by the American Lung Association (ACRC Network)

Published by: Journal of Asthma, July 2017

Study: The purpose of the current study was to determine if obesity is associated with increased severity of sinonasal disease, and/or affects response to nasal corticosteroid treatment in asthma. It was concluded that obesity does not affect severity of sinonasal disease in patients with asthma. Severity of sinonasal disease was associated with increased asthma severity regardless of BMI (Body Mass Index. Body mass index (Body Mass Index. Body mass index (BMI) is a measure of body fat based on height and weight.) The response of obese patients to nasal corticosteroids requires further study as the efficacy of this treatment might be reduced in obesity.

The study was funded by the American Lung Association (ACRC Network) and the National Heart Blood and Lung Institute

Published by: The Annals of the American Thoracic Society, July 2018

Study: Anxiety is a common co-morbidity of Chronic Obstructive Pulmonary Disease (COPD) that is associated with higher morbidity and mortality. This study from the American Lung Association's Airways Clinical Research Center Network evaluated three anxiety screening questionnaires, to evaluate and compare how they perform in COPD patients.

Results: Symptoms of anxiety among COPD patients as identified by screening questionnaires were common and significantly higher than the prevalence of anxiety disorder meeting by DSM-V criteria. The GAD-7, the HADS and the AIR questionnaires had fair to moderate psychometric properties as screening tools for anxiety in individuals with COPD, indicating the need for improved measures for this patient population.

The study was funded by the American Lung Association (ACRC Network) 

Published by: The Annals of the American Thoracic Society, online July 2016

Study: This study from the American Lung Association's Airways Clinical Research Center Network, looked at whether continuous positive airway pressure (CPAP) reduced airways reactivity in asthma. Short-term studies of CPAP in asthma patients had previously shown reductions in airways reactivity in those using CPAP.

Results: Adherence to nocturnal CPAP was low and there was no evidence to support positive pressure as effective for reducing airways reactivity in people with well controlled asthma. Regardless, airways reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airways reactivity and merits further investigation.

The study was co-funded by the American Lung Association (ACRC Network) and the National Heart, Lung, and Blood Institute (NHLBI).

Published by: Journal of the American Medical Association (May 26, 2015)

Study: This study from the American Lung Association's Airways Clinical Research Centers (ACRC) Networks looked at whether soy isoflavone—a common nutritional supplement—improves the health of people with poor asthma control. During the study, adults and children aged 12 years and older who have poorly controlled asthma took a controller medication. Some study participants also took a soy isoflavone supplement while others took a placebo in place of soy isoflavone.

Results: The study found that the soy isoflavone supplement did not improve participants' lung function or clinical outcomes. The results may save consumers from spending thousands of dollars on an ineffective treatment, and also potentially helped some avoid adverse drug reactions.

The study was co-funded by the American Lung Association (ACRC Network) and the National Heart, Lung, and Blood Institute (NHLBI).

Published by: Journal of Allergy and Clinical Immunology (2014)

Study: The network's ninth study, Study of Nasal Steroids in Asthma examined whether long-term treatment of sinonasal disease with mometasone improved asthma control, lung function and quality of life in patients aged 6 years and older with poorly controlled asthma and chronic rhinitis/sinusitis. In previously conducted ACRC trials, researchers have found that more than 70 percent of asthmatics report sinusitis, rhinitis or both.

Results: The study found no difference between those taking mometasone versus a placebo in the improvement of their asthma control. Children and adolescents (age 6 to 17 years) experienced no difference in their asthma or sinus symptoms, but those taking mometasone (versus the placebo) did experience a decrease in their lung function. Adult participants who took mometasone showed a small difference in asthma symptoms measured by using the Asthma Symptom Utility Index and in nasal symptoms, but they didn't experience a difference in asthma quality of life, lung function, or episodes of poorly controlled asthma.

This study was funded by the National Institute of Health's National Heart, Lung and Blood Institute.

Published by: Journal of Allergy and Clinical Immunology (2014)

Study: This study evaluated whether methacholine challenge in subjects ages 12 to 70 with stable asthma is a sensitive test to diagnose or confirm asthma. The study also looked at whether using high-potency inhaled corticosteroids (ICS) alters methacholine responsiveness.

Results: Results indicated that the methacholine test may not be a reliable tool for conclusively excluding the diagnosis of asthma and that it should not be used as the sole method of diagnosis, especially in white and nonatopic (non allergic)  patients. African-American patients were more sensitive to methacholine challenge than whites (95 percent versus 69 percent, respectively). Additionally, the sensitivity was 82 percent in those with atopy, defined as having one or more positive allergy skin test results, compared with 52 percent in those without. There was no significant difference in the change for high- vs low-dose ICS.

Published by: Journal of the American Medical Association (2012)

Study: The Study of Acid Reflux in Children with Asthma (SARCA) is similar to the SARA protocol described below, but focused on the connection between asthma and gastroesophageal reflux (GERD), and looked at whether treatments for GERD decreased asthma flare-ups in children.

Results: The results of this study found that taking heartburn medication along with asthma treatments did not improve symptoms nor lung function, and were was associated with increased undesirable side effects.

This study was funded by the National Institute of Health's National Heart, Lung and Blood Institute.

Published by: The New England Journal of Medicine (2009)

Study: The Study of Acid Reflux and Asthma (SARA) examined whether there was a connection between asthma and gastroesophageal reflux (GERD). It examined whether treatments for GERD decreased asthma flare-ups in adults.

Results: The results of this study found the longstanding practice of prescribing heartburn medication to be ineffective and unnecessarily expensive for some asthma patients who do not exhibit symptoms associated with acid reflux such as heartburn or stomach pain. This finding is considered to be the most comprehensive evaluation to date of how effective (or ineffective) prescription heartburn medication is at controlling respiratory flare-ups in people with asthma whose symptoms have not been well controlled by other therapies. Based on results from both these studies, roughly 1.5 million asthma patients may be taking expensive medication unnecessarily. For people with asthma currently using a preventative asthma medication, the use of proton pump inhibitors in patients shown to actually have acid reflux instead of all patients with poorly controlled asthma could save over $1.1 billion a year in health care expenditures.

This study was funded by the National Institute of Health's National Heart, Lung and Blood Institute.

Published by: Allergy Clin Immunol 2009;124:445-6.

The Trial of Patient Education and Asthma. The purpose of this research study was to investigate the way that educational approaches and presentation of a drug may affect the response to montelukast and placebo (an inactive medication) in subjects with asthma.  Information that enhances expectations about drug effectiveness improves the response to placebos for pain. Although asthma symptoms often improve with placebo, it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit.

The study objective was to determine whether response to placebo or a leukotriene antagonist (montelukast) can be augmented by messages that increase expectation of benefit. Methods: A randomized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups. Participants were randomly assigned to one of 4 treatment groups in a factorial design.  Optimistic drug presentation augments the placebo effect for patient-reported outcomes (asthma control) but not lung function. However, the effect of montelukast was not enhanced by optimistic messages.

This study was funded by the National Institute of Health's National Heart, Lung and Blood Institute and the American Lung Association.

Published by: Chest: The Cardiopulmonary and Critical Care Journal (2009)

Study: The network's fifth study, Sinusitis and Rhinitis in Asthma was designed to determine whether treatment for sinusitis would improve asthma control.

Results: The results of the study identified a simple and reliable five-item questionnaire, based on the frequency of nasal symptoms, to accurately screen for sinonasal disease. The use of this tool is expected to significantly reduce the need for expensive CT scans and invasive endoscopy.

Published by: Journal of Allergy and Clinical Immunology (2009)

Study: The Trial of Asthma Patient Education examined whether patient education and the method of presenting asthma drugs improved the treatment response to both placebo (inactive) and active asthma medications.

Results: The results of this study showed that neither the presence of a placebo nor enhancing patients' expectancy about the effectiveness of a drug had an effect on lung function. However, study participants in the placebo-with-enhanced-messages group reported an improvement in their asthma symptoms despite no improvement in lung function. The placebo effect is a well-documented phenomenon among patients; doctors' conversations with study participants can drastically impact a study's results and should be carefully considered.

This study was funded by the National Institute of Health's National Heart, Lung and Blood Institute.

Published by: The New England Journal of Medicine (2007)

Study: Leukotriene Modifier or Corticosteroid or Corticosteroid-Salmeterol Trial examined whether treatment for patients with mild asthma that was well controlled with the use of low-dose inhaled corticosteroids twice daily, could be stepped down to an alternative, less intensive treatment strategy—either combination therapy or leukotriene modifier—without a loss of asthma control.

Results: The study found that a simpler regimen of a once-a-day combination therapy of inhaled fluticasone plus salmeterol was just as effective as twice-daily treatment of inhaled corticosteroids in patients with mild, persistent asthma. The leukotriene modifier, oral montelukast, while not as effective, did provide good control for most patients. For people with asthma, a simpler treatment plan means fewer drugs to take (and to remember to take) every day and fewer prescription refills. Overall, this reduces medication costs, reduces side effects and makes it easier for people to take their medication as prescribed.  For people with asthma who are at least 6 years old and currently using a preventative medication, the use of once-daily fluticasone plus salmeterol, instead of twice-daily fluticasone could save almost $2 billion per year.

Published by: American Journal of Respiratory and Critical Care Medicine (2007)

Study: Effectiveness of Low Dose Theophylline as Add-On Therapy in Treatment of Asthma examined whether low-dose theophylline could be used safely and effectively as an alternative to the widely used add-on therapy, montelukast. Low-dose theophylline is a relatively inexpensive asthma medicine that has fallen out of favor in recent years because of concerns about its side effects.

Results: The study found that low-dose theophylline did not help people improve control of their asthma as an add-on therapy (when asthma is not well controlled, doctors may add on additional therapies to help patients better control their symptoms). However, low-dose theophylline was a useful alternative for people who were not able or willing to take inhaled corticosteroids, an often-used asthma treatment. These results offer immediate clinical data for physicians treating patients who are unable or unwilling to use inhaled corticosteroids. For people with asthma not currently using a preventative asthma medication, the use of theophylline instead of montelukast could save about $800 million a year.

Published by: The New England Journal of Medicine (2001)

Study: The Study of Inactivated Influenza Vaccine in Asthmatics examined the effect of the influenza vaccination on people with asthma. It was the first large randomized study that examined the effect of the influenza vaccination on people with asthma.

Results: The study found that influenza vaccines are safe for both children and adults with asthma. Based on these American Lung Association findings, The Centers for Disease Control and Prevention now recommends flu shots for children with asthma in the Advisory Committee on Immunization Practices of the Centers for Disease Control recommendations and The Healthy People 2020 Goals. Administering the flu vaccine to people with asthma has the potential to majorly reduce hospitalizations and increase cost savings. The Lung Association estimates that if 100 percent of people with asthma were vaccinated, approximately 59,000 adult hospitalizations would be avoided, at a cost savings of close to $569 million. An estimated 45,000 children would avoid hospitalization, saving $182 million.