A clinical trial that will test a novel treatment for asthma has begun enrolling patients.
The treatment — semaglutide — is a medication approved to help control blood sugar in people with Type 2 diabetes and for weight management in obese or overweight adults. Semaglutide is one of seven approved GLP-1 receptor agonists that target a metabolic pathway to increase insulin secretion and improve glycemic control.
“Our trial represents the first prospective study of this class of medications in individuals with asthma,” said Katherine Cahill, MD, assistant professor of Medicine and medical director of Clinical Asthma Research at Vanderbilt University Medical Center. Cahill and Gordon Bernard, MD, Melinda Owen Bass Professor of Medicine and director of the Vanderbilt Institute for Clinical and Translational Research (VICTR), are co-principal investigators of the clinical trial.
The researchers will test semaglutide in adult patients who have symptomatic asthma and who are obese (BMI>/=30). They plan to enroll 100 patients at VUMC, who will be randomized to receive semaglutide or a placebo.
Comorbid obesity impacts about 40% of adults with asthma.
“Patients with asthma and comorbid obesity respond less well to our standard of care, which is inhaled corticosteroids, have more asthma symptoms, and are at greater risk for hospitalizations,” Cahill said. “Additionally, they have metabolic changes that may be worsened by the administration of steroids, whether inhaled or oral, which we use for asthma exacerbations (acute flares).”
Cahill noted that the prevalence of asthma with comorbid obesity is rapidly increasing nationally and globally.
“Hopefully, using this class of medications that targets a metabolic pathway, which has never been done in asthma, will provide benefit to patients with asthma and comorbid obesity and eliminate some of the unintended side effects of steroid medications,” she said. The clinical trial follows a series of basic science studies at VUMC led by R. Stokes Peebles, MD, and Kevin Niswender, MD, PhD. With colleagues Melissa Bloodworth, MD, PhD, and Shinji Toki, PhD, they demonstrated in preclinical animal models of asthma that GLP-1 receptor agonists reduced lung inflammation and improved lung responses to challenges like allergies and viruses.
These preclinical findings prompted Cahill, who at the time was a faculty member at Brigham and Women’s Hospital, to use electronic health record data to identify patients with asthma and Type 2 diabetes who initiated treatment with a GLP-1 receptor agonist or another diabetes medication — and to examine asthma symptoms in these patients.
Cahill and her colleagues found that in the six months after starting a Type 2 diabetes medication, individuals who received GLP-1 receptor agonists had lower rates of asthma exacerbations and reduced asthma symptoms compared to individuals who initiated other types of diabetes medications.
“The preclinical and electronic health record data supported moving forward with the current phase 2 trial,” said Cahill, who joined the VUMC faculty in 2018 and has secured funding for the trial from the National Institute of Allergy and Infectious Diseases.
The research team worked with VICTR to design a program that searches electronic health records for patients who fit the inclusion/exclusion criteria for the study, and who can be contacted through My Health at Vanderbilt. The Vanderbilt Coordinating Center is helping with patient recruitment and enrollment, and the study will be conducted at the Vanderbilt Asthma, Sinus & Allergy Program clinic.
The study includes a four-week monitoring period prior to treatment, 24 weeks of semaglutide (weekly subcutaneous injection) or matched placebo, and two weeks of follow-up monitoring. Asthma symptoms will be assessed using a standardized asthma control questionnaire, and researchers will collect blood, airway samples and adipose tissue to explore the impact of semaglutide on inflammation.
Semaglutide has been approved for individuals who are overweight or obese and do not have Type 2 diabetes.
“We’re optimistic that if we identify evidence of clinical benefit in asthma with obesity, we can move to overweight individuals with asthma and possibly even into lean individuals with asthma in the future,” Cahill said.
By targeting a metabolic pathway that regulates inflammation across multiple organ systems, the study could mark a paradigm shift in the approach to treating asthma, she said.
Co-investigators joining Cahill and Bernard for the trial include:
- Bloodworth, who completed her MD and PhD at Vanderbilt and is now an Allergy & Immunology clinical research fellow
- Peebles, Elizabeth and John Murray Professor of Medicine
- Niswender, associate professor of Medicine and director of the Clinical Research Center
- Leonard Bacharier, MD, Janie Robinson and John Moore Lee Professor of Pediatrics
- Pingsheng Wu, PhD, research professor of Medicine
- William Dupont, PhD, professor of Biostatistics
The GATA-3 study (GLP-1 Receptor Agonist in the Treatment of Adult, Obesity-related, Symptomatic Asthma) is supported by a grant from the National Institutes of Health (AI155299). The pharmaceutical company Novo Nordisk is providing semaglutide and matched placebo for the study. For more information and to learn how to participate, visit https://www.tnasthmaobesitystudy.com/
