Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology

NCT05757583 | Recruiting DMC

• 2 other identifiers: 22-37338R01HL164787
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center study of 80 subjects with asthma including those with obesity and metabolic dysfunction (MD), those with obesity and without metabolic dysfunction, those with severe asthma and mucus plugging and those with severe asthma and without mucus plugging. Screening data will be reviewed to determine participant eligibility. Participants who meet all inclusion criteria will participate in a cardiopulmonary exercise testing (CPET) visit to compare lung function markers and change in oxygen saturation between obese patients with and without MD and severe asthma patients with and without mucus plugging.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change in EELV (End Expiratory Lung Volume)

  We will compare change in EELV during the CPET (Cardiopulmonary Exercise Test) between the obese asthma patients with MD or without MD and between the patients with severe asthma with mucus plugs or without mucus plugs.

  At CPET visit.

Secondary Outcomes (2)

• Change in RV (Residual Volume) and TLC (Total Lung Capacity)

  At CPET Visit

• Change in oxygen saturation during exercise

  At CPET Visit

Study Arms (4)

Patients with asthma, obesity and metabolic dysfunction

Otherwise healthy asthmatic subjects with: 1. Body Mass Index (BMI) ≥ 30; and 2. Metabolic dysfunction evidenced by at least one of the following: * high plasma IL-6 (\> 3.0 pg/mL) * insulin resistance (HOMA-IR \> 3 mass units)

Patients with asthma, obesity and no metabolic dysfunction

Otherwise healthy asthmatic subjects with: 1. Body Mass Index (BMI) ≥ 30; and 2. No evidence of metabolic dysfunction

Patients with severe asthma and mucus plugs

Otherwise healthy asthmatic subjects: 1. Requiring treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy; and 2. Evidence of mucus plugs as defined by a mucus plug score ≥ 4

Patients with severe asthma and no mucus plugs

Otherwise healthy asthmatic subjects: 1. Requiring treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy; and 2. No evidence of mucus plugs as defined by a mucus plug score \< 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will recruit up to 80 asthma participants, at least 20 with obesity and MD, 20 with obesity and no MD, 20 with severe asthma and mucus plugs and 20 with severe asthma and no mucus plugs.

You may qualify if:

• Male or female ≥ 18 years old at Visit 0
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
• History of physician diagnosed asthma
• Evidence of bronchodilator reversibility (12% improvement in FEV1 after albuterol administration) or positive methacholine challenge PC20 or PD20. Historical evidence is accepted.
• Meets criteria for obesity or severe asthma a. Obesity: BMI≥30 i. Metabolic dysfunction is defined as presence of either:
• \. IL-6 high: Plasma IL-6 \> 3.0 pg/mL 2. Insulin resistance: HOMA-IR \> 3 mass units b. Severe asthma: Requires treatment with high dose inhaled corticosteroids plus a second controller, systemic corticosteroid, or biologic therapy.
• i. Mucus Plugging is defined as mucus plug score ≥ 4

You may not qualify if:

• Asthma exacerbation or URI within the previous 6 weeks.
• History of smoking
• If \<30 years old: Smoked for ≥5 pack-years
• If ≥30: Smoked for ≥10 pack years
• Pregnancy
• Absolute or relative contraindication to exercise testing per ATS criteria
• Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician of record.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UCSF Airway Clinical Research Center

San Francisco, California, 94143, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples of plasma and serum will be banked in the UCSF Airway Tissue Bank.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• John Fahy, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade Vi, BS

CONTACT

415-476-1783; jade.vi@ucsf.edu

John Fahy, MD, MS

CONTACT

415-476-9940; john.fahy@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 7, 2023
• Study Start: April 5, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)