Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

Obesity Clinical Trial

Official title:

Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03215836
• Other study ID #: 16-2522
• Status: Recruiting
• Phase: N/A
• Start date: August 10, 2017
• Est. completion date: December 31, 2029

Study information

• Verified date: February 2023
• Source: University of Colorado, Denver
• Contact: Asthma Research
• Phone: 1 (844) 365-0852
• Email: asthmaresearch[@]ucdenver.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2029
• Est. primary completion date: March 10, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 (all groups):

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.

Related Conditions & MeSH terms

• Asthma
• Metabolic Syndrome
• Obesity

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Jewish Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of L-arginine-NO biosynthesis pathways in the airway epithelium in obese and non-asthmatics.	L-arginine-NO biosynthesis pathways will be measured in the airway epithelium of mild to moderate controlled obese and non-obese asthmatics with metabolic syndrome by ELISA and western blot analysis.	Within 6 months of collection
Primary	Measurement of oxidative stress in the airway epithelium in obese and non-asthmatics.	Oxidative stress will be measured in the airway epithelium of mild to moderate controlled obese and non-obese asthmatics without metabolic syndrome by Griess Reaction and western blot analysis.	Within 6 months of collection
Secondary	Measurement of mitochondrial density	Mitochondrial density will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.	Within 6 months of collection
Secondary	Measurement of mitochondrial structural differences.	Mitochondrial structural differences will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.	Within 6 months of collection
Secondary	Patterns of Gene expression found in the nasal epithelium.	Nasal epithelial cells will be obtained by one time nasal brushings and gene expression patterns will be evaluated.	Within 6 months of collection