Adiposity and Airway Inflammation in HIV-Associated Airway Disease

Asthma Clinical Trial

— SHOP  

Official title:

Adiposity and Airway Inflammation in HIV-Associated Airway Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02975258
• Other study ID #: PRO15070529
• Secondary ID: 1R56HL128134-01A
• Status: Completed
• Phase: N/A
• First received: November 1, 2016
• Last updated: October 11, 2017
• Start date: September 2015
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goals of this study are to 1) examine the relationships among inflammation, obesity, and asthma in people with HIV and 2) to test if special subtypes of cells or markers are present in the blood and lungs of people with HIV with asthma compared to those without asthma.

Description:

The proposed study involves the recruitment of participant population and the use of data from the existing research study cohorts that have been recruited and have provided informed consent for participation. Participants meet all inclusion/exclusion criteria will be enrolled into the study. Participants in the existing research study cohorts have pulmonary function testing, chest CT scans, and blood draws at each study visit which occurs every 18 months for 3 visits. Some of the study procedures may not be repeated if they were done as part of other research projects.

1. Main study visit

The following research procedures may be performed over the course of one or more visits to accommodate scheduling needs. The study visit will take place at the Montefiore Clinical and Translational Research Center and the University of Pittsburgh Asthma Institute in the University of Pittsburgh Medical Center - Montefiore Hospital and may take up to 4 hours to complete.

• Informed consent

• Medical history review and demographics

• Review of inclusion/exclusion criteria

• Physical examination to include vital signs, weight and height, waist, hip, and thigh circumferences.

• Urine pregnancy test for female of childbearing potential

• Asthma-focused and quality of life questionnaire

• Exhaled Nitric Oxide (eNO) measurement

• Spirometry

• Methacholine challenge testing - will not need to be repeated if the participant had done this as part of another study in the past 6 months.

• Chest/Abdominal CT scans (If the participant has had the Chest CT scan done within 6 months as part of other research study, they will not be repeated for study purposes. Only the Abdominal CT will be performed)

• Research blood sampling for biomarker analyses - some of this blood will also be used for pre-bronchoscopy testing in the case that the participant qualifies and is interested in undergoing part 2, the bronchoscopy visit.

• Adipose tissue biopsy (Fat Biopsy): performed on participants with a BMI≥25). This will be repeated if done previously because testing to be done on the fat will be different than what had been tested on the fat previously.

2. Optional sub-study

On a separate visit, only a subset of 60 selected participants will be asked to undergo the following procedures to obtain additional lung biological samples. This visit is optional for participants who are willing to participate in the bronchoscopy portion. The investigators will try to recruit an equal number (n=15 per group) of obese asthmatics, obese non-asthmatics, non-obese asthmatics, and non-obese non-asthmatics. The visit will take place in the Montefiore Clinical Translational Research Center (MUH-CTRC). The bronchoscopy procedure will take about 30-45 minutes, but the preparation and recovery time will usually make the visit about 4-8 hours total.

Participants will be expected to fast for 8 hours prior to the bronchoscopy procedure and refrain from drinking any liquids the day of the procedure. Participants may take their usual medicines with sips of water.

• Clinical laboratory testing to include complete blood count/differential/platelet count, prothrombin time/partial thromboplastin time, international Normalized Ratio, blood urea nitrogen, and creatinine prior to bronchoscopy. If the patient refuses the first blood draw, the sample is inadequate, or the labs were run more than 30 days prior to the bronchoscopy visit, a second blood sample of up to 1 tablespoon may be drawn prior to the bronchoscopy procedure to ensure the patient is healthy enough for the procedure.

If Methacholine challenge was done more than 30 days prior to the visit two date, pulmonary function tests will be repeated.

• Oral Wash: participants will be asked to gargle with salt water for 1 minute and then spit into a container to provide a sample of approximately 10mls (2 teaspoons) at this study visit.

• Tongue Scraping: tongue blade or similar object will be used to scrape the participant's tongue. This sample will be used to determine what bacteria are on the participant's tongue. This procedure should only take minutes and is not painful.

• Participants will then rinse with 10cc's of Listerine. This is to assure that there are no bacteria left behind in the participant's mouth prior to the bronchoscopy.

• Bronchoscopy with bronchoalveolar lavage (BAL), endobronchial brushing and biopsy

Under local anesthesia, participants will undergo bronchoscopy with BAL for microbiologic specimens. A light intravenous anesthetic will be titrated to provide participant comfort if necessary. Vitals signs will be monitored continuously before, during, and after the procedure. This procedure consists of 3 stages.

1. Pulmonary Lavage: During pulmonary lavage, five 50 mL washes of sterile salt-water solution will be injected through the bronchoscope. Fluid will be collected with gentle suctioning for research studies.

2. Bronchial Brushing: A small brush will be introduced through the bronchoscope and gently rubbed over a very small part of the surface of the lungs. Approximately 10 brushes will be performed to collect epithelial cells.

3. Endobronchial Biopsy: While the bronchoscope is inserted, another small instrument will be passed through the bronchoscope to take small samples (biopsies) of tissue from the walls of the airways. Up to 5 samples may be taken during this procedure.

Following the bronchoscopy procedure, participants will be closely monitored in the bronchoscopy recovery area or return to the CTRC. Rarely, the participant's asthma may worsen during or after the procedure. Appropriate medical treatments or overnight observation will be provided if needed. Participants will not be allowed to drive home after the bronchoscopy. This is because the sedatives used during the procedure may decrease driving ability. The investigators will ask for the contact name and number of the person that will pick up the participant after the bronchoscopy

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. 18 years of age or older

2. Subject who have been previously determined to be HIV positive through testing

Exclusion Criteria:

1. Pregnancy or breast-feeding

2. Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.)

3. Heart condition such as tachycardia, angina or arrhythmias

4. Acute respiratory infection: increasing respiratory symptoms or fever (temperature >100.4°F [38°C]) within 4 weeks of study entry

5. Hospitalization within 4 weeks of study entry

6. Uncontrolled hypertension at screening visit (systolic > 160 mm Hg or diastolic > 100 mm Hg) from an average of two or more readings (participant may return for screening after blood pressure is controlled)

7. Active cancer requiring systemic chemotherapy or radiation

8. Active infection of lungs, brain, or abdomen; or intravenous drug use or alcohol use that will impair ability to complete study investigations in the opinion of the investigator

9. History of prior lung resection

Related Conditions & MeSH terms

• Adiposity
• Asthma
• HIV
• Inflammation
• Obesity

Intervention

Procedure:
• Blood draw
Blood will be drawn for plasma, serum, and peripheral blood mononuclear cells.

Other:
• Questionnaires
The following questionnaires are administered to participants by study personnel: Gingo Asthma Questionnaire (GAQ) and the Asthma Quality of Life questionnaire (AQL).

Procedure:
• Spirometry
Spirometry is a simple breathing test that measures the amount of air in one's lungs and how well one can move that air by forcefully blowing 3 or more times into a mouthpiece. A series of these maneuvers will be performed under the instruction of a respiratory technician or respiratory therapist.
• Methacholine challenge test
A methacholine challenge is a common test often used to support a diagnosis of asthma. The test consists of inhaling increasing doses of methacholine through a nebulizer to assess how quickly the participant's airways narrow.

Radiation:
• Quantitative CT scans
There will be a standard chest CT and an abdominal CT. The CT scans capture contiguous volume scans acquired at slice thicknesses of 5.0 mm in the axial plane and reconstructed with 512 x 512 pixel matrices. CT examinations will encompass the entire thorax and the abdomen and will be performed during a breath-hold at end-inspiration. The investigators will measure % of lung tissue below a threshold for emphysema (i.e. -950 Hounsfield units). Measurements have been histologically-verified and give reproducible measurements. The data set is assembled and analyzed with the image data anonymized. If the participant has had a research chest CT scan done recently, only the abdomen CT will be done.

Procedure:
• Urine pregnancy test
All female participants with childbearing potential will be asked to provide a urine sample for pregnancy testing. The result of the pregnancy test must be negative in order for her to be in this research study.
• Adipose biopsy
The doctor will obtain a sample of fat cells from the participant's abdomen. Numbing medicine will be applied. A needle is placed through the skin & into the fat pad under the skin. A blunt-tip hollow cannula is then used to aspirate fat tissue through the incision.
• Exhaled nitric oxide measurement
The investigators will measure concentrations of exhaled nitric oxide by asking the participant to inhale deeply, and then exhale very slowly into a mouthpiece for between 10-15 seconds.

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse interaction of adiposity and HIV-associated inflammation in asthma susceptibility and airway remodeling in HIV	The investigator will test association of adiposity (body mass index, waist circumference, computed tomography (CT)-measured visceral adiposity) with prevalence of asthma and longitudinal progression of airway obstruction. the blood and lungs of people with HIV with asthma compared to those without asthma.	Baseline
Secondary	Correlation between leptin and asthma susceptibility in HIV.	Leptin, an obesity-related inflammatory marker, levels will be compared between HIV+ asthmatics and non-asthmatics and correlated with airway remodeling on endobronchial biopsy and CT.	Baseline
Secondary	Correlation between adiponectin, asthma susceptibility, and airway remodeling in HIV.	Adiponectin, an obesity-related inflammatory marker, levels will be compared between HIV+ asthmatics and non-asthmatics and correlated with airway remodeling on endobronchial biopsy and CT.	Baseline
Secondary	Adipose tissue-related inflammation contributes to asthma susceptibility and airway remodeling in HIV.	Using abdominal adipose tissue biopsies, the investigators will phenotype adipose-specific inflammatory cells and pathways and determine associations with asthma, airway remodeling, and longitudinal progression of airway obstruction.	Baseline
Secondary	Low L-arginine increases asthma risk and airway remodeling in HIV.	The investigator will measure L-arginine in serum and bronchoalveolar lavage samples to compare levels between HIV+ asthmatics and non-asthmatics and correlate L-arginine with CT and biopsy measures of airway remodeling.	Baseline
Secondary	Low ADMA increases asthma risk and airway remodeling in HIV.	The investigator will measure ADMA in serum and bronchoalveolar lavage samples to compare levels between HIV+ asthmatics and non-asthmatics and correlate ADMA with CT and biopsy measures of airway remodeling.	Baseline