Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes

NCT ID: NCT02238327

Last Updated: 2020-10-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

232 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-09-30

Study Completion Date

2020-03-02

Brief Summary

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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

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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

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Chronic Obstructive Pulmonary Disease HIV Emphysema

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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HIV positive normal pulmonary function

HIV positive DLCO percent predicted \>=.80 FEV1/FVC percent predicted \>=0.70

blood draw

Intervention Type PROCEDURE

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

questionnaires

Intervention Type PROCEDURE

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

Lung function testing

Intervention Type PROCEDURE

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 test

Intervention Type PROCEDURE

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 scans

Intervention Type RADIATION

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 collection

Intervention Type PROCEDURE

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.

Echocardiogram

Intervention Type PROCEDURE

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

HIV positive with pulmonary dysfuntion

HIV positive DLco percent predicted \<=0.80% FEV1/FVC percent predicted\<=0.70%

blood draw

Intervention Type PROCEDURE

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

questionnaires

Intervention Type PROCEDURE

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

Lung function testing

Intervention Type PROCEDURE

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 test

Intervention Type PROCEDURE

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 scans

Intervention Type RADIATION

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 collection

Intervention Type PROCEDURE

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.

Echocardiogram

Intervention Type PROCEDURE

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

Interventions

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blood draw

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

Intervention Type PROCEDURE

questionnaires

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

Intervention Type 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.

Intervention Type 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.

Intervention Type PROCEDURE

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.

Intervention Type RADIATION

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.

Intervention Type PROCEDURE

Echocardiogram

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

Intervention Type PROCEDURE

Other Intervention Names

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Spirometry CT scan of the chest Nasal wash Nasal scrapping Echo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role lead

Responsible Party

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Alison Morris

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26372280 (View on PubMed)

Gingo 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.

Reference Type BACKGROUND
PMID: 29313714 (View on PubMed)

Qin 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.

Reference Type BACKGROUND
PMID: 30286195 (View on PubMed)

Other Identifiers

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1R01HL125049-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO14070355

Identifier Type: -

Identifier Source: org_study_id

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