Chronic Obstructive Pulmonary DiseaseLEAPNCT02238327
Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes
An observational study of Chronic Obstructive Pulmonary Disease and HIV, run by University of Pittsburgh at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, HIV, Emphysema
- What is being tested?
- blood draw, questionnaires and Lung function testing
- Type of treatment
- Surgery or procedure
- How many people
- 232 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to 2 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: The Study is a Multicenter, Prospective Observational Study of Pathogenesis of HIV Pulmonary Disease.
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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease, HIV, Emphysema
- Being tested
- blood draw, questionnaires, Lung function testing, Six-Minute walk test, Quantitative CT scans
- Keywords
- Antiretroviral therapy, pulmonary function, biomarkers
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Emphysema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood drawProcedure or surgery
Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.
questionnairesProcedure or surgery
The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.
Lung function testingProcedure or surgery
Also called Spirometry
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.
Six-Minute walk testProcedure or surgery
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.
Quantitative CT scansRadiation
Also called CT scan of the chest
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.
Nasal secretion and cell collectionProcedure or surgery
Also called Nasal wash, Nasal scrapping
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.
EchocardiogramProcedure or surgery
Also called Echo
The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.
| Study group | Role | What they receive |
|---|---|---|
| HIV positive normal pulmonary function | HIV positive DLCO percent predicted >=.80 FEV1/FVC percent predicted >=0.70 Receives: 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 | |
| HIV positive with pulmonary dysfuntion | HIV positive DLco percent predicted <=0.80% FEV1/FVC percent predicted<=0.70% Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
differences in the trajectory of FEV1 in clinical COPD phenotypes,
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.
Measured: 36 months
Secondary outcomes (1)
will measure biomarkers of these phenotypes and ability to predict HIV COPD
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion2 Mar 2020
- Study completion2 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Alison Morris, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02238327
- Sponsor's protocol ID
- PRO14070355
- Other IDs
- 1R01HL125049-01
- Acronym
- LEAP
- Status last verified
- Oct 2020
- First submitted
- 4 Sep 2014
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, Rom W, Weiden MD, Zhao E, Thompson B, Crothers K. Factors associated with abnormal spirometry among HIV-infected individuals. AIDS. 2015 Aug 24;29(13):1691-700. doi: 10.1097/QAD.0000000000000750.
PubMed 26372280Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.
PubMed 29313714Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, Huang L, Ghedin E, Greenblatt RM, Morris A. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018 Oct 4;13(10):e0205065. doi: 10.1371/journal.pone.0205065. eCollection 2018.
PubMed 30286195
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study is a Multicenter, Prospective Observational Study of Pathogenesis of HIV Pulmonary Disease.
- ClinicalTrials.gov ID
- NCT02238327
- Acronym / sponsor ID
- LEAP / PRO14070355
- Conditions
- Chronic Obstructive Pulmonary Disease, HIV, Emphysema
- Keywords
- Antiretroviral therapy, pulmonary function, biomarkers
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2014 (actual)
- Primary completion
- 2 Mar 2020 (actual)
- Study completion
- 2 Mar 2020 (actual)
- First posted
- 12 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV positive normal pulmonary function | – | 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: EchocardiogramHIV positive DLCO percent predicted >=.80 FEV1/FVC percent predicted >=0.70 |
| HIV positive with pulmonary dysfuntion | – | 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: EchocardiogramHIV positive DLco percent predicted <=0.80% FEV1/FVC percent predicted<=0.70% |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood drawBlood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| questionnairesThe following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| Lung function testingAlso: SpirometryThe 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. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| Six-Minute walk testSix-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. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| Quantitative CT scansAlso: CT scan of the chestSubjects 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. | Radiation | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| Nasal secretion and cell collectionAlso: Nasal wash, Nasal scrappingParticipants 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. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
| EchocardiogramAlso: EchoThe cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging. | Procedure or surgery | HIV positive normal pulmonary function, HIV positive with pulmonary dysfuntion |
Primary outcome
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.
1 secondary outcome
will measure biomarkers of these phenotypes and ability to predict HIV COPD
Time frame: 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Background: PubMed 26372280Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, Rom W, Weiden MD, Zhao E, Thompson B, Crothers K. Factors associated with abnormal spirometry among HIV-infected individuals. AIDS. 2015 Aug 24;29(13):1691-700. doi: 10.1097/QAD.0000000000000750.
- Background: PubMed 29313714Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.
- Background: PubMed 30286195Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, Huang L, Ghedin E, Greenblatt RM, Morris A. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018 Oct 4;13(10):e0205065. doi: 10.1371/journal.pone.0205065. eCollection 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Obstructive Pulmonary Disease and HIV, run by University of Pittsburgh at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
differences in the trajectory of FEV1 in clinical COPD phenotypes, (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02238327, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.