Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology

Asthma Clinical Trial

— IMAP  

Official title:

Impact of Metabolic Dysfunction and Mucus Plugging on Asthma Physiology

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05757583
• Other study ID #: 22-37338
• Secondary ID: R01HL164787
• Status: Recruiting
• Start date: April 5, 2023
• Est. completion date: April 2025

Study information

• Verified date: June 2023
• Source: University of California, San Francisco
• Contact: Xavier Orain, BS
• Phone: 415-502-3472
• Email: xavier.orain[@]ucsf.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The mechanism of poor exercise tolerance in patients with severe asthma is poorly understood. In preliminary data, the investigators have identified increases in air trapping in patients with obese asthma and metabolic dysfunction and patients with asthma and mucus plugs. The investigators have also found air trapping on CT (Computerized Tomography) scans of severe asthma patients with mucus plugs. Therefore, the investigators hypothesize that obese patients with metabolic dysfunction (MD) and severe asthma patients with mucus plugs develop changes in lung function during exercise.

To test this hypothesis, this protocol will plan for cardiopulmonary exercise testing in patients with obesity or severe asthma. The analyses will compare dynamic hyperinflation, expiratory flow limitation, and the RV/TLC ratio (ratio of residual volume to total lung capacity) before and after exercise between obese patients with and without MD and severe asthma patients with and without mucus plugs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female = 18 years old at Visit 0

2. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

3. History of physician diagnosed asthma

4. Evidence of bronchodilator reversibility (12% improvement in FEV1 after albuterol administration) or positive methacholine challenge PC20 or PD20. Historical evidence is accepted.

5. Meets criteria for obesity or severe asthma a. Obesity: BMI=30 i. Metabolic dysfunction is defined as presence of either:

1. 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

Exclusion Criteria:

1. Asthma exacerbation or URI within the previous 6 weeks.

2. History of smoking

1. If <30 years old: Smoked for =5 pack-years

2. If =30: Smoked for =10 pack years

3. Pregnancy

4. Absolute or relative contraindication to exercise testing per ATS criteria

5. Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician of record.

Related Conditions & MeSH terms

• Asthma

Locations

Country	Name	City	State
United States	UCSF Airway Clinical Research Center	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in RV (Residual Volume) and TLC (Total Lung Capacity)	We will compare change in RV and TLC during the CPET 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	Change in oxygen saturation during exercise	Change in oxygen saturation during the CPET will be assessed and compared 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