Glucagon-Like Peptide-1 Receptor Agonist in the Treatment of Adult, Obesity-related, Symptomatic Asthma (GATA-3)

• Status: Not yet recruiting
• Trial end date: 2026-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized placebo-controlled trial of semaglutide, an FDA-approved therapy for the treatment of type 2 diabetes mellitus and obesity, in adults with symptomatic asthma despite the use of inhaled steroids and with excess body weight. We will test the central hypothesis that semaglutide will improve asthma control and reduce airway inflammation due to direct effects on the respiratory tract in adult asthma associated with obesity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)

Criteria

Inclusion Criteria:

1. Subject must be able to understand and provide informed consent.

2. Males and females age 18 or older

3. Obesity defined as body mass index (BMI) ≥30

4. History of physician-diagnosed asthma

5. Persistent Asthma as determined by the requirement of at least medium-dose daily inhaled corticosteroid or more

6. Symptomatic asthma with an ACQ-6 score ≥1.5 at enrollment and at the time of randomization

7. Patient report of stable asthma controller regimen for the prior 8 weeks

8. Evidence of bronchodilator responsiveness (≥12% and at least 200 mL increase in FEV1) or airway hyperresponsiveness with a Methacholine PC20 ≤8 mg/mL

9. Female subjects of childbearing potential must have a negative pregnancy test upon study entry

10. Female subjects of childbearing potential must agree to use a highly effective birth control method (e.g. hormonal, surgical or abstinence) for the duration of the study

Exclusion Criteria:

At enrollment:

1. Inability or unwillingness of a subject to give written informed consent or comply with the study protocol

2. Diagnosis of type I or type II diabetes mellitus (DM) or HbA1c ≥6.5 on screening labs

3. Use of >8 puffs/inhalations of short-acting bronchodilators most days in the previous week (I.e. answer to question #6 on ACQ-6 = 4, 5, or 6)

4. Oxygen saturation < 94% on room air

5. Patient-reported Tobacco, e-cigarette, or smoked marijuana use within 12 months, or >10 years of use

6. Pregnancy by urine testing, current lactation, or plans to become pregnant during the study period

7. Pharmaceutical or lifestyle weight loss treatment in the prior 90 days at enrollment

8. Previous surgical weight loss treatment

9. Personal history of pancreatitis as determined by history

10. Personal or family history of medullary thyroid cancer by history or multiple endocrine neoplasia syndrome type 2

11. Personal history of gallstone disease without previous cholecystectomy

12. Personal history of gastroparesis

13. Personal history of hypersensitivity to semaglutide

14. Personal history of hypersensitivity to local amide type (ex. Lidocaine) anesthetics

15. Use of metformin or any other antidiabetic agent including GLP-1R agonist in the previous 90 days

16. Use of systemic glucocorticoids in the past 28 days

17. Use of monoclonal antibody for the treatment of asthma in the past 120 days

18. Myocardial infarction, unstable angina, stroke, or heart failure (NYHA class II) within 1 year by history

19. History of other physician-diagnosed chronic respiratory diseases: COPD, cystic fibrosis, pulmonary hypertension, interstitial lung disease, sarcoidosis, bronchiectasis by patient report

20. History of physician-diagnosed immune deficiency.

21. History of physician-diagnosed malignancy (other than excised non-melanoma skin cancer) in the past 5 years.

22. Current uncontrolled hypertension (systolic >150, diastolic >90) or untreated hyperthyroidism

23. Current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements.

24. Use of investigational drugs within 20 weeks of participation, other than vaccines and/or treatments for SARS-CoV-2 authorized for emergency use

25. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

At randomization:

26. Screening creatinine elevation with EGFR<60 collected at visit 1a

27. Compliance to baseline asthma inhaler therapy of <80% during run-in, at the time of randomization.