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Glucagon-Like Peptide-1 Receptor Agonist Treatment in Adult, Obesity-Related, Symptomatic Asthma

Award Number: U01AI155299
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Glucagon-Like Peptide-1 Receptor Agonist Treatment in Adult, Obesity-Related, Symptomatic Asthma - Project Summary Obesity is clearly detrimental in asthma, yet we lack tools to treat the unique obese asthma phenotype. Comorbid obesity impacts >40% of adult asthmatics1 and increases asthma severity, symptoms and exacerbations while simultaneously reducing the efficacy of conventional therapies.2-5 Our long-term goal is to develop novel treatments for airway inflammation in the obese asthma phenotype. Our overall objective, which is the next step in translating our preclinical and preliminary clinical findings, is to determine the impact of glucagon-like peptide-1 receptor agonists (GLP-1RA) on asthma control and airway and adipose inflammation in adults with obese asthma. Our central hypothesis is that GLP-1RA improve asthma control and reduce airway inflammation due to direct effects on the respiratory tract in obese asthma. To generate the proof-of- concept data to support definitive phase 3 clinical trials of GLP-1RA in the obese asthma phenotype and test our central hypothesis, we propose the following specific aims: 1) Determine the efficacy of GLP-1RA on asthma control and assess tolerability in obese asthma and 2) Determine the tissue-specific impact of GLP- 1RA on inflammation in the airway and adipose in obese asthma. In a 12-week double-blind, randomized, placebo-controlled trial of oral semaglutide 7 mg once daily in adult subjects with obesity-related, symptomatic asthma without DMII, we will test the hypotheses that semaglutide improves asthma control (aim 1a), is tolerated (aim 1b) and reduces type-2 and non-type 2 airway inflammation independent of weight loss (aim 2). The primary clinical outcome will be change from baseline in ACQ-7. The primary mechanistic outcome will be change from baseline in serum periostin. Because insulin resistance is variable in obesity and baseline blood eosinophil counts are often predictive of response to asthma therapeutics, these markers will be used for prespecified subgroup analyses. Subcutaneous abdominal adipose and respiratory tract samples at baseline and 5 and 12 weeks of therapy will be compared using RNA sequencing to test the hypothesis that GLP-1RA reduce inflammation to restore homeostasis in the respiratory tract opposite to changes in adipose tissue in obese asthma. This proposal facilitates the collection of the necessary clinical, mechanistic, and tolerability data to inform the design of a definitive phase III clinical trial of a GLP-1RA in asthma. It thereby supports the rapid development of a novel therapeutic class for asthma and represents a paradigm shift in the approach to therapeutic intervention in asthma through the targeting of a metabolic pathway which regulates upstream inflammation across multiple organ systems, may be disease modifying, and ultimately glucocorticoid sparing.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $1,583,667 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	5	4/28/2025	NON-COMPETING CONTINUATION	$1,583,667
														Subtotal = $1,583,667

Issue Date FY: 2024 ( Subtotal = $1,583,667 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	001	4	5/2/2024	NON-COMPETING CONTINUATION	$1,583,667
2024	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	3	11/30/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,583,667

Issue Date FY: 2023 ( Subtotal = $1,583,667 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	001	3	5/17/2023	NON-COMPETING CONTINUATION	$1,583,667
2023	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	2	12/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,583,667

Issue Date FY: 2022 ( Subtotal = $1,583,667 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	2	4/12/2022	NON-COMPETING CONTINUATION	$1,583,667
														Subtotal = $1,583,667

Issue Date FY: 2021 ( Subtotal = $1,583,667 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	1	4/28/2021	NEW	$1,583,667
														Subtotal = $1,583,667

Grand Total All Awards = $7,918,335

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Glucagon-Like Peptide-1 Receptor Agonist Treatment in Adult, Obesity-Related, Symptomatic Asthma

Award Number: U01AI155299

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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