by Leigh Macmillan
A clinical trial that will test a new 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 to control weight in overweight or obese 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 drug class in people with asthma,” he said. Katherine Cahill, MD, assistant professor of medicine and medical director of Clinical Asthma Research at Vanderbilt University Medical Center. Cahill and Gordon BernardMD, 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 investigators will evaluate 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 semaglutide or placebo.
Comorbid obesity affects approximately 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 higher risk for hospitalizations,” Cahill said. “In addition, they have metabolic changes that can be made worse by steroids, either inhaled or oral, that we use for asthma exacerbations (acute flare-ups).”
Cahill noted that the prevalence of asthma with comorbid obesity is increasing rapidly nationally and globally.
“Hopefully, using this class of drugs that target 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 unwanted side effects of drugs.” steroids,” he said. The clinical trial follows a series of basic science studies in the VUMC led by R. Stokes PeeblesMD, and kevin niswender, MD, PhD. With her 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 such as allergies and viruses.
These preclinical findings led Cahill, who at the time was a faculty member at Brigham and Women’s Hospital, to use electronic medical record data to identify patients with asthma and type 2 diabetes who started treatment with a GLP-1 receptor agonist. or other diabetes medication. and to examine asthma symptoms in these patients.
Cahill and his colleagues found that in the six months after starting a medication for type 2 diabetes, people who received GLP-1 receptor agonists had lower rates of asthma exacerbations and a reduction in asthma symptoms compared with people who Other types of diabetes medication were started.
“Preclinical and electronic health record data supported the advancement of the current phase 2 trial,” said Cahill, who joined the VUMC faculty in 2018 and obtained 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 of patients who meet the study’s inclusion/exclusion criteria and who can be contacted through My Health at Vanderbilt. The Vanderbilt Coordinating Center is assisting with patient recruitment and enrollment, and the study will take place at the Vanderbilt Asthma, Sinus and Allergy Program clinic.
The study includes a four-week pretreatment control period, 24 weeks of semaglutide (weekly subcutaneous injection) or matching placebo, and two weeks of follow-up control. Asthma symptoms will be assessed using a standardized asthma control questionnaire, and researchers will collect blood, airway, and adipose tissue samples to explore semaglutide’s impact on inflammation.
Semaglutide has been approved for people 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 people with asthma and possibly even lean people with asthma in the future,” Cahill said.
By targeting a metabolic pathway that regulates inflammation in multiple organ systems, the study could mark a paradigm shift in the approach to treating asthma, he said.
Co-investigators who joined Cahill and Bernard for the trial include:
- Bloodworth, who completed her MD and PhD at Vanderbilt and is now a Clinical Research Fellow in Allergy and Immunology.
- Peebles, Elizabeth and John Murray Professor of Medicine
- Niswender, associate professor of medicine and director of the Center for Clinical Research
- 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 (GLP-1 Receptor Agonist in the Treatment of Symptomatic Obesity-Related Asthma in Adults) study is supported by a grant from the National Institutes of Health (AI155299). The pharmaceutical company Novo Nordisk is providing semaglutide and a matching placebo for the study. For more information and to find out how to get involved, visit https://www.tnasthmaobesitystudy.com/