Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

NCT03215836 | Recruiting

• 1 other identifier: 16-2522
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Obesity; Metabolic Syndrome

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Measurement of mitochondrial density

  Within 6 months of collection

• Measurement of mitochondrial structural differences.

  Within 6 months of collection

• Patterns of Gene expression found in the nasal epithelium.

  Within 6 months of collection

Study Arms (4)

Obese Asthmatics

OTHER

BMI \>/= 30 and without metabolic syndrome

Procedure: Bronchoscopy and Nasal Epithelium Brush Sampling

Obese Astmatics

OTHER

BMI \>/= 30 and with metabolic syndrome

Procedure: Bronchoscopy and Nasal Epithelium Brush Sampling

Obese non-asthmatics

OTHER

BMI \>/= 30

Procedure: Bronchoscopy and Nasal Epithelium Brush Sampling

Non - obese asthmatics

OTHER

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

Procedure: Bronchoscopy and Nasal Epithelium Brush Sampling

Interventions

Bronchoscopy and Nasal Epithelium Brush Sampling 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; Obese Asthmatics; Obese Astmatics; Obese non-asthmatics

Eligibility Criteria

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

You may qualify if:

• For ALL Groups
• Adequate completion of informed consent process with written documentation
• Male and female patients, ≥ 18 - 65 years old
• 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.
• Specific to Asthma Groups
• i. From all racial/ethnic backgrounds with a diagnosis of asthma based on physician diagnosis for \>6 months
• 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.
• 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.
• 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.

You may not qualify if:

• 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);
• Chronic renal failure (creatinine \> 2.0) at screening (associated with higher asymmetric dimethylarginine (ADMA) levels);
• Current statins use (statins lower ADMA levels);
• On diabetic medications;
• Positive pregnancy test;
• Positive urine cotinine and/or urine tetrahydrocannabinol (THC) test;
• Current or recent (within 30 days) investigational treatment or participation in another interventional research study (including non-pharmacologic interventions);
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Jewish Health: collaborator

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Asthma; Obesity; Metabolic Syndrome

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Fernando Holguin, MD, MPH

  University of Colorado Denver, Anschutz Medical Campus

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asthma Research

CONTACT

1 (844) 365-0852; asthmaresearch@ucdenver.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 (BMI ≥ 30) asthmatics without metabolic syndrome, 2. Obese asthmatics with metabolic syndrome, 3. Obese non-asthmatics, and 4. Non - obese (lean \> 18 \<= 25, OW \> 25 - \<30) asthmatics.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: July 12, 2017
• Study Start: August 10, 2017
• Primary Completion (Estimated): March 10, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 2, 2023

Record last verified: 2023-02

Locations

US (1)