Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes

HIV Clinical Trial

— LEAP  

Official title:

The Study is a Multicenter, Prospective Observational Study of Pathogenesis of HIV Pulmonary Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02238327
• Other study ID #: PRO14070355
• Secondary ID: 1R01HL125049-01
• Status: Completed
• Start date: September 2014
• Est. completion date: March 2, 2020

Study information

• Verified date: October 2020
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: March 2, 2020
• Est. primary completion date: March 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Emphysema
• HIV
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Procedure:
• blood draw
Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.
• questionnaires
The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.
• 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.
• 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.

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

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, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	36 months
Secondary	will measure biomarkers of these phenotypes and ability to predict HIV COPD		36 months