Clinical Trials

MainTitle

Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes (LEAP)

This study is currently recruiting participants. (see Contacts and Locations)

Verified October 2017 by Alison Morris, University of Pittsburgh

Sponsor
University of Pittsburgh

Collaborator
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party)
Alison Morris, University of Pittsburgh

ClinicalTrials.gov Identifier
NCT02238327

First received: September 4, 2014
Last updated: October 2, 2017
Last Verified: October 2017
History of Changes
Purpose

Purpose

The overall hypotheses of this proposal are that discrete phenotypes of HIV Chronic Obstructive Pulmonary disease (COPD) differ in their trajectories, biomarkers, and risk factors and that persistent viral infection including residual HIV is linked to HIV COPD.

Condition Intervention
Chronic Obstructive Pulmonary Disease
HIV
Emphysema

Procedure : blood draw
Procedure : questionnaires
Procedure : Lung function testing
Procedure : Six-Minute walk test
Radiation : Quantitative CT scans
Procedure : Nasal secretion and cell collection
Procedure : Echocardiogram

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Study is a Multicenter, Prospective Observational Study of Pathogenesis of HIV Pulmonary Disease.

Further study details as provided by Alison Morris, University of Pittsburgh:

Primary Outcome Measures

  • differences in the trajectory of FEV1 in clinical COPD phenotypes, [ Time Frame: 36 months ]
    PFT's at baseline, 18 months and 36months to determine modifying risk factors and relationship of phenotypes to mortality, and delineate the association of ART and lung dysfunction.
Secondary Outcome Measures:
  • will measure biomarkers of these phenotypes and ability to predict HIV COPD [ Time Frame: 36 months ]

Biospecimen Retention: Samples With DNA
Whole blood, serum, bronchial wash and cells

Estimated Enrollment: 200
Study Start Date: September 2014
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
HIV positive normal pulmonary function
HIV positive DLCO percent predicted >=.80 FEV1/FVC percent predicted >=0.70
Procedure: blood draw

Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.

Procedure: questionnaires

The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.

Procedure: Lung function testing

The routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured before and after bronchodilator administration (4 puffs of albuterol). The best of three reproducible forced expiratory attempts is used in analysis. Percent- predicted spirometric values are based on age, height, gender, and ethnicity. DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms to ATS standards. DLco will be adjusted for hemoglobin and carboxyhemoglobin.

Other Name: Spirometry
Procedure: Six-Minute walk test

Six-minute walk tests are performed in a 100 foot (30.48 m) segment of straight hallway marked at 10 foot (3 m) intervals. In addition to the usual ATS protocol, the patient is monitored, when available, with Bluetooth wireless pulse oximetry and the time and distance recorded after six minutes and if they desaturate to <88%. Dyspnea (Borg 0-10) and perceived exertion (Borg 6-20) scales are completed at the beginning and the end of test.

Radiation: Quantitative CT scans

Subjects will undergo a standard chest CT. The CT scans will use a phantom shipped between sites to standardize results and 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 be performed during a breath-hold at end-inspiration. We 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.

Other Name: CT scan of the chest
Procedure: Nasal secretion and cell collection

Participants will be instructed to blow their nose to remove accumulated mucus. Two sprays of commercially available nasal saline will be instilled in each nostril. The participant will then be ask to exhale through the rinsed nostril into a specimen cup. We will repeat this up to 5 times on each side depending on the participants' tolerance to the procedure. Using an otoscope, a small curette will then be used to collect 3 to 5 samples of nasal cells from each nostril. These samples will be used immediately for analysis or banked for future study.

Other Name:
  • Nasal wash
  • Nasal scrapping

Procedure: Echocardiogram

The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.

Other Name: Echo
HIV positive with pulmonary dysfuntion
HIV positive DLco percent predicted <=0.80% FEV1/FVC percent predicted<=0.70%
Procedure: blood draw

Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.

Procedure: questionnaires

The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.

Procedure: Lung function testing

The routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured before and after bronchodilator administration (4 puffs of albuterol). The best of three reproducible forced expiratory attempts is used in analysis. Percent- predicted spirometric values are based on age, height, gender, and ethnicity. DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms to ATS standards. DLco will be adjusted for hemoglobin and carboxyhemoglobin.

Other Name: Spirometry
Procedure: Six-Minute walk test

Six-minute walk tests are performed in a 100 foot (30.48 m) segment of straight hallway marked at 10 foot (3 m) intervals. In addition to the usual ATS protocol, the patient is monitored, when available, with Bluetooth wireless pulse oximetry and the time and distance recorded after six minutes and if they desaturate to <88%. Dyspnea (Borg 0-10) and perceived exertion (Borg 6-20) scales are completed at the beginning and the end of test.

Radiation: Quantitative CT scans

Subjects will undergo a standard chest CT. The CT scans will use a phantom shipped between sites to standardize results and 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 be performed during a breath-hold at end-inspiration. We 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.

Other Name: CT scan of the chest
Procedure: Nasal secretion and cell collection

Participants will be instructed to blow their nose to remove accumulated mucus. Two sprays of commercially available nasal saline will be instilled in each nostril. The participant will then be ask to exhale through the rinsed nostril into a specimen cup. We will repeat this up to 5 times on each side depending on the participants' tolerance to the procedure. Using an otoscope, a small curette will then be used to collect 3 to 5 samples of nasal cells from each nostril. These samples will be used immediately for analysis or banked for future study.

Other Name:
  • Nasal wash
  • Nasal scrapping

Procedure: Echocardiogram

The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.

Other Name: Echo

Detailed Description:

The study is a multicenter, prospective observational study of pathogenesis of HIV pulmonary disease. We will determine the prevalence and risk factors for lung dysfunction as quantified by pulmonary function testing in HIV+ subjects. We will build on our existing longitudinal cohorts while adjusting for important co-variates such as antiretroviral therapy (ART), smoking history, co-infections, and illicit drug use. Evaluations will be scheduled at baseline, 18 months, and 36 months. (6, 12, 18 and 36 months for ART initiators at the UCSF). Study visits will consist of blood draw, questionnaires, pulmonary function testing, 6-minute walk test, CT of the chest at visit two. Oral specimen collection and glycocalyx and echocardiogram (visit two) at the Pittsburgh site only.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 80 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  
Sampling Method: Probability Sample  

Study Population

The study population will be HIV positive subjects previously seen for other studies. There will be three centers enrolling, the University of Pittsburgh, the University of California San Francisco, and the University of California Los Angeles. Recruitment will occur from participants in ongoing lung studies at these sites.

Criteria

Inclusion Criteria:

  • HIV-1 infection, documented in medical record at any time prior to study entry.
  • Men and women age 18 to 80.
  • Ability and willingness to complete all tests.
  • Participant in HLRC studies, MACS, Women's Interagency Health Study, and local HIV clinics.
  • For UCSF only, new ART initiators from Women's Interagency Health Study or the HIV clinic


Exclusion Criteria:
  • Pregnancy or breast-feeding.
  • Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
  • Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4 weeks of study entry.
  • Hospitalization within 4 weeks prior to study entry (excluding mental health).
  • Uncontrolled hypertension at screening visit (systolic > 180 mm Hg or diastolic > 100 mm Hg) from an average of two or more readings. Subject may return for screening after blood pressure is controlled.
  • Active cancer requiring systemic chemotherapy or radiation.
  • Active infection of lungs, brain, or abdomen.
  • Intravenous drug use or alcohol use that will impair ability to complete study
investigations in the opinion of the investigator

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02238327

Locations

United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Cathy J Kessinger, RN    412-624-8330    kessingercj@upmc.edu
Sub-Investigator: Cathy Kessinger, RN

Sponsors and Collaborators

University of Pittsburgh
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
More Information

More Information


Responsible Party: Alison Morris, Professor, University of Pittsburgh  
ClinicalTrials.gov Identifier: NCT02238327   History of Changes  
Other Study ID Numbers: PRO14070355  
  1R01HL125049-01  
Study First Received: September 4, 2014  
Last Updated: October 2, 2017  

Keywords provided by Alison Morris, University of Pittsburgh:

Antiretroviral therapy
pulmonary function
biomarkers

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Emphysema

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.