search
Back to results

Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

Primary Purpose

Asthma, Obesity, Metabolic Syndrome

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Bronchoscopy and Nasal Epithelium Brush Sampling
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Asthma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of ColoradoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Other

Other

Other

Arm Label

Obese Asthmatics

Obese Astmatics

Obese non-asthmatics

Non - obese asthmatics

Arm Description

BMI >/= 30 and without metabolic syndrome

BMI >/= 30 and with metabolic syndrome

BMI >/= 30

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Measurement of mitochondrial density
Mitochondrial density will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.
Measurement of mitochondrial structural differences.
Mitochondrial structural differences will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.
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.

Full Information

First Posted
June 12, 2017
Last Updated
February 1, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Jewish Health
search

1. Study Identification

Unique Protocol Identification Number
NCT03215836
Brief Title
Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics
Official Title
Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 10, 2017 (Actual)
Primary Completion Date
March 10, 2027 (Anticipated)
Study Completion Date
December 31, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Jewish Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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: Obese (Body Mass Index (BMI) ≥ 30) asthmatics without metabolic syndrome, Obese asthmatics with metabolic syndrome, Obese non-asthmatics, and 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma, Obesity, Metabolic Syndrome

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model 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: Obese (BMI ≥ 30) asthmatics without metabolic syndrome, Obese asthmatics with metabolic syndrome, Obese non-asthmatics, and Non - obese (lean > 18 <= 25, OW > 25 - <30) asthmatics.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Obese Asthmatics
Arm Type
Other
Arm Description
BMI >/= 30 and without metabolic syndrome
Arm Title
Obese Astmatics
Arm Type
Other
Arm Description
BMI >/= 30 and with metabolic syndrome
Arm Title
Obese non-asthmatics
Arm Type
Other
Arm Description
BMI >/= 30
Arm Title
Non - obese asthmatics
Arm Type
Other
Arm Description
BMI: lean > 20; Normal >/= 20 to <25; overweight </= 25 to < 30;
Intervention Type
Procedure
Intervention Name(s)
Bronchoscopy and Nasal Epithelium Brush Sampling
Intervention Description
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.
Primary Outcome Measure Information:
Title
Measurement of L-arginine-NO biosynthesis pathways in the airway epithelium in obese and non-asthmatics.
Description
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.
Time Frame
Within 6 months of collection
Title
Measurement of oxidative stress in the airway epithelium in obese and non-asthmatics.
Description
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.
Time Frame
Within 6 months of collection
Secondary Outcome Measure Information:
Title
Measurement of mitochondrial density
Description
Mitochondrial density will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.
Time Frame
Within 6 months of collection
Title
Measurement of mitochondrial structural differences.
Description
Mitochondrial structural differences will be measured from cells obtained by one time pulmonary lavage during bronchoscopy.
Time Frame
Within 6 months of collection
Title
Patterns of Gene expression found in the nasal epithelium.
Description
Nasal epithelial cells will be obtained by one time nasal brushings and gene expression patterns will be evaluated.
Time Frame
Within 6 months of collection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria (all groups): 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Asthma Research
Phone
1 (844) 365-0852
Email
asthmaresearch@ucdenver.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando Holguin, MD, MPH
Organizational Affiliation
University of Colorado Denver, Anschutz Medical Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asthma Research
Phone
844-365-0852
Email
asthmaresearch@ucdenver.edu

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Airway epithelial cells, serum samples and bronchoalveolar lavage (BAL) fluid and BAL cells being collected under this protocol will be collected in UC Denver and sent to National Jewish Hospital (NJH) as per agreed protocols. Specimens/instruments will be completely de-identified and the only data that will be sent to Hong Wei Chu's lab at National Jewish Hospital (NJH) will be specimens labeled with a code.

Learn more about this trial

Obesity, Metabolic Dysregulation and the Airway Epithelium in Asthmatics

We'll reach out to this number within 24 hrs