Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

NCT ID: NCT03215836

Last Updated: 2023-02-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-10
• Study Completion Date: 2029-12-31

Brief Summary

The objective of this pilot study is to determine whether obesity and metabolic syndrome are in fact synergistic in relation to airway nitric oxide (NO) biology. To do so, the investigators want to determine how obesity and the metabolic syndrome relate to metabolism in bronchial airway epithelial cells and the nasal epithelium.

Detailed Description

This is a cross sectional pilot study comparing specific metabolic pathways in bronchial airway epithelial cells and the nasal epithelium across the following patient groups:

1. Obese (Body Mass Index (BMI) ≥ 30) asthmatics without metabolic syndrome,

2. Obese asthmatics with metabolic syndrome,

3. Obese non-asthmatics, and

4. Non - obese (lean > 18 <= 25, Overweight (OW) > 25 - <30) asthmatics.

Participants in these groups will be matched by gender, age and asthma severity. To be enrolled, participants must be non-current smokers and be controlled. After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Participants without a bronchodilator withhold will be scheduled to undergo a methacholine test. Those that qualify will undergo a bronchoscopy to obtain bronchoalveolar lavage and airway epithelial cells and nasal epithelial brush sampling for gene expression studies. After the procedure is done and post bronchoscopy safety standards are met, participants will be discharged from the inpatient Clinical Translational Research Center (CTRC) recovery area. The research coordinator will call the participant on the night of the procedure and on the next day to document post-procedure clinical stability.

Conditions

Asthma; Obesity; Metabolic Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Obese Asthmatics

BMI \>/= 30 and without metabolic syndrome

Group Type: OTHER

Bronchoscopy and Nasal Epithelium Brush Sampling

Intervention Type: PROCEDURE

After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Obese Astmatics

BMI \>/= 30 and with metabolic syndrome

Group Type: OTHER

Bronchoscopy and Nasal Epithelium Brush Sampling

Intervention Type: PROCEDURE

After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Obese non-asthmatics

BMI \>/= 30

Group Type: OTHER

Bronchoscopy and Nasal Epithelium Brush Sampling

Intervention Type: PROCEDURE

After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Non - obese asthmatics

BMI: lean \> 20; Normal \>/= 20 to \<25; overweight \</= 25 to \< 30;

Group Type: OTHER

Bronchoscopy and Nasal Epithelium Brush Sampling

Intervention Type: PROCEDURE

After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Interventions

Bronchoscopy and Nasal Epithelium Brush Sampling

After meeting screening criteria, participants will undergo further evaluation to determine whether or not inclusion and exclusion criteria are met. Participants will undergo a baseline evaluation, lung function testing and a subsequent bronchoscopy and nasal epithelial brush sampling in those that meet study enrollment.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

For ALL Groups

1. Adequate completion of informed consent process with written documentation

2. Male and female patients, ≥ 18 - 65 years old

3. Smoking history <10 pack years and no smoking in the last year

**Subjects can be included in the study if they are on blood pressure treatment and are on a diet control/exercise only treatment of diabetes.

4. Specific to Asthma Groups

i. From all racial/ethnic backgrounds with a diagnosis of asthma based on physician diagnosis for >6 months

1. Specific to Metabolic Syndrome Group. Metabolic syndrome diagnosis based on having at least any three of: a. Triglycerides ≥ 150 mg/dl; b. High-density lipoproteins (HDL) cholesterol ≤ 50 mg/dl for women and ≤ 40 mg/dl for men; c Fasting blood glucose ≥ 100 mg/dl; d. Waist circumference > 40 inches males and > 35 inches females); e. Previously diagnosed hypertension or on antihypertensive medication; f. Blood pressure greater than 130/85 on two consecutive measurements.

2. Specific to Non-Metabolic Syndrome Group a. Baseline pre-bronchodilator forced expiratory volume (FEV1) of 50% or greater of predicted with a 12% or greater bronchodilator (BD) response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response; b. BMI ≥ 30

Metabolic syndrome diagnosis based on having at least any three of:

i. Triglycerides ≥ 150 mg/dl; ii. HDL cholesterol ≤ 50 mg/dl for women and ≤ 40 mg/dl for men; iii. Fasting blood glucose ≥ 100 mg/dl; iv. Waist circumference > 40 inches males and > 35 inches females); v. Previously diagnosed hypertension or on antihypertensive medication; vi. Blood pressure greater than 130/85 on two consecutive measurements.

3. Specific to Non-Obese Group a. Body Mass Index (BMI) < 30

b. Specific to Non-Asthma Group i. No history of asthma or any other airway diseases; ii. Pulmonary function test within normal limits; iii. BMI ≥ 30.

Exclusion Criteria

1. Significant or uncontrolled concomitant medical illness (PI discretion) including, but not limited to heart disease, cancer, diabetes (HbAc1 > 6.5), renal disease (creatinine > 2.0) at Visit 0, neurological (brain damage) or psychiatric disorder (diagnosed by a mental health professional of behavioral or mental pattern that may cause suffering or a poor ability to function in life);

2. Chronic renal failure (creatinine > 2.0) at screening (associated with higher asymmetric dimethylarginine (ADMA) levels);

3. Current statins use (statins lower ADMA levels);

4. On diabetic medications;

5. Positive pregnancy test;

6. Positive urine cotinine and/or urine tetrahydrocannabinol (THC) test;

7. Current or recent (within 30 days) investigational treatment or participation in another interventional research study (including non-pharmacologic interventions);

8. Unable or unlikely to complete study assessments or the study intervention (i.e. bronchoscopy) poses undue risk to patient in the opinion of the investigator.

a. Specific to Asthma Groups i. Respiratory tract infection within the last 4 weeks; ii. Oral or systemic corticosteroids (CS) burst within the last 4 weeks; iii. Asthma-related hospitalization within the last 2 months; iv. Asthma-related ER visit within the previous 4 weeks.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Jewish Health

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fernando Holguin, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Colorado Denver, Anschutz Medical Campus

Locations

University of Colorado

Aurora, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Asthma Research

Role: CONTACT

asthmaresearch@ucdenver.edu

1 (844) 365-0852

Facility Contacts

Asthma Research

Role: primary

asthmaresearch@ucdenver.edu

844-365-0852

Other Identifiers

16-2522

Identifier Type: -

Identifier Source: org_study_id