Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)

NCT03572335 | Completed DMC

• 1 other identifier: STUDY19050326
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Diffusing capacity for carbon monoxide (DLco) abnormalities are common in HIV+ individuals and associated with significant morbidity and mortality. The complexity and the individualized differences in causes of these abnormalities have been challenging to unravel using traditional approaches. In this proposal, the investigators construct a systems' modeling approach to identify novel molecular and clinical pathways contributing to DLco impairment in HIV+ individuals and to determine predictive signatures of DLco decline in order to develop strategies to treat and prevent abnormal lung function in this susceptible population.

Conditions

HIV Infections; Pulmonary Disease

Keywords

HIV; emphysema; diffusing capacity; chronic obstructive pulmonary disease(COPD)

Outcome Measures

Primary Outcomes (1)

• Identify key causal molecular pathways of DLco impairment.

  elucidating complex associations and causal relationships between clinical characteristics, the host inflammatory response, cellular metabolism, the microbiome, and miRNAs.

  3 years

Study Arms (2)

HIV positive with normal PFT's

HIV positive with normal baseline DLco. Subjects with DLco\>80% predicted after adjustments for Hgb and Co

Diagnostic Test: PFT's (pulmonary function testing)

HIV positive with mild DLco impairment

HIV positive with mild DLco impairment DLco \<80% predicted after adjustments for Hgb and Co.

Diagnostic Test: PFT's (pulmonary function testing)

Interventions

PFT's (pulmonary function testing) DIAGNOSTIC_TEST

The routine lung function endpoints of FVC(forced vital capacity), FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder before and after bronchodilator administration. The system is calibrated for body temperature and pressure of saturated gas and volumes, per American Thoracic Society (ATS) standards . DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms with ATS standards.

Also known as: 6MWT (6 minute walk test)

HIV positive with mild DLco impairment; HIV positive with normal PFT's

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

18-80 year old men and women who are HIV positive. All will be pulled from previous HIV/Lung studies done by the same PI

You may qualify if:

• Men and women age 18 to 80
• HIV positive and participated in previous HLRC(HIV Lung Research Center) study (PRO10060177, PRO09050521, PRO14070355, PRO08030011, PRO00606151, PRO13050229, PRO17060077).
• Negative pregnancy test (for women of child barring capabilities).
• Have undergone bronchoscopy with BAL(bronchial lavage) and/or brushing for AECs in storage.
• Receiving ART (Anti-Retroviral Therapy)and virally-suppressed for at least 6 months.

You may not qualify if:

• Pregnancy or breast-feeding. (urine pregnancy done on all females of child bearing potential-males and females who are at least 1 year post menopausal or surgically sterile will not be tested)
• 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.
• Acute cardiopulmonary issue in the past 4 months.
• 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.
• subjects with an upper or lower respiratory tract infection
• individuals receiving chronic or acute antibiotics in the prior 4 months.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh department of medicine division of Pulmonary, Allergy and Critical Care medicine

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, saliva, oral wash, stool

MeSH Terms

Conditions

HIV Infections; Lung Diseases; Emphysema; Pulmonary Disease, Chronic Obstructive

Interventions

Respiratory Function Tests; Walk Test

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Exercise Test; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Officials

• Alison Morris, MD, MS

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: June 28, 2018
• Study Start: September 6, 2018
• Primary Completion: October 1, 2022
• Study Completion: August 1, 2024
• Last Updated: March 7, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)