HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by Weill Medical College of Cornell University
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT02056158
First received: February 4, 2014
Last updated: January 13, 2015
Last verified: January 2015
  Purpose

In HIV+ cigarette smokers, with no prior history of pulmonary infections, emphysema is often developed at an earlier age and is a significant cause of morbidity despite treatment with antiretroviral drugs. Preliminary data gathered from HIV+ individuals that smoke cigarettes strongly support the hypothesis that the combination of HIV infection and smoking creates increased stress in the lower respiratory tract. To examine the underlying factors that contribute to the accelerated development of emphysema in this cohort, samples from the lower respiratory tract will be provided by HIV+ and HIV- subjects. The samples collected will serve as biomarkers for assessing the onset of emphysema.


Condition
HIV
COPD
Emphysema
Smoking

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Changes in oxidant stress in the lower respiratory tract in association with HIV infection and smoking [ Time Frame: One year ] [ Designated as safety issue: No ]
    Using samples obtained from subjects the extent and nature of the HIV/smoking-induced oxidant burden of the lower respiratory tract will be assessed.


Biospecimen Retention:   Samples With DNA

Blood samples and biopsies from the lower respiratory tract.


Estimated Enrollment: 480
Study Start Date: December 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts
HIV Negative Early COPD Smokers
HIV Negative Early COPD Smokers
HIV Negative COPD Smokers
HIV Negative COPD Smokers
HIV Negative Nonsmokers
HIV Negative Nonsmokers
HIV Negative Smokers
HIV Negative Smokers
HIV Positive Smokers
HIV Positive Smokers
HIV Positive Nonsmokers
HIV Positive Nonsmokers
HIV Positive COPD Smokers
HIV Positive COPD Smokers
HIV Positive Early COPD Smokers
HIV Positive Early COPD Smokers

Detailed Description:

The purpose of this study is to analyze biologic samples from the blood, airways and/or urine of HIV- and HIV+ smokers and non-smokers to better understand the etiology and pathogenesis of emphysema in association with HIV infection. The underlying hypothesis is that the combination of HIV infection and smoking creates chronic oxidant stress in the lower respiratory tract that promotes cellular loss and contributes to the progressive development of emphysema. Preliminary data strongly supports our hypothesis that the accelerated development of emphysema among HIV+ smokers is due in part to the interaction of HIV directly on the macrophage found in the pulmonary alveolus. The interaction causes a release of exaggerated amounts of oxidants in the lower respiratory tract and leads to increased levels of oxidized metabolites. HIV+ individuals with emphysema have high plasma levels of apoptotic pulmonary capillary-derived micro particles that contain oxidized metabolites. The increased release of micro particles is characteristic of an apoptotic process.

We will study this hypothesis by sampling HIV+ and HIV‾ subjects alveolar macrophages (AM), which are found on the epithelial surface of the lung, and epithelial lining fluid (ELF) found in the lower respiratory tract. We will also assess plasma pulmonary capillary-derived endothelial microparticles (EMPs) as a biomarker for pulmonary apoptosis. Using newly developed mass spectrometry methodologies, we will quantify the oxidant stress of AM, ELF and plasma EMPs, and identify specific oxidized metabolites within each of these compartments. Finally, we will examine the interaction in vitro to tease apart the contribution of each component (AM, ELF, and plasma EMPs) of the interaction.

To assess this concept, the following aims will be addressed:

Specific Aim 1 (n=160). To explore the extent of the oxidant stress in the lower respiratory tract in association with HIV infection and smoking.

Specific Aim 2 (n=160). To evaluate plasma levels of capillary apoptosis and oxidation state of HIV+ nonsmokers and smokers.

Specific Aim 3 (n=160). To examine the interaction of pulmonary capillary endothelium and various oxidant effector components to identify oxidant-vulnerable pathways relevant to the development of new treatment therapies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

New York Metropolitan area residents

Criteria

Inclusion Criteria:

HEALTHY VOLUNTEER RESEARCH SUBJECTS

  • All study subjects should be able to provide informed consent
  • Males or females ages 18 years and older
  • Must provide HIV informed consent

VOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE

  • Must provide informed consent
  • Males and females age 18 years and older
  • Lung disease proven by at least one of the following: symptoms consistent with pulmonary disease; (2) chest X-rays consistent with lung disease; (3) pulmonary function tests consistent with lung disease; (4) lung biopsy consistent with lung disease; (5) family history of lung disease; and/or (6) diseases of organs with known association with lung disease
  • Must provide HIV informed consent

Exclusion Criteria:

HEALTHY VOLUNTEER RESEARCH SUBJECTS

  • Individuals not deemed in good overall health by the investigator will not be accepted into the study.
  • Habitual use of drugs and/or alcohol within the past six months (Acceptable: - Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria).
  • Individuals with history of chronic lung disease, including asthma or with recurrent or recent (within three months) acute pulmonary disease will not be accepted into the study.
  • Individuals with allergies to atropine or any local anesthetic will not be accepted into the study.
  • Individuals with allergies to pilocarpine, isoproterenol, terbutaline, atropine or aminophylline will not be accepted into the study.
  • Females who are pregnant or nursing will not be accepted into the study

VOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE

  • Any history of allergies to xylocaine, lidocaine, versed, valium, atropine, pilocarpine, isoproterenol, terbutaline, aminophylline, or any local anesthetic will not be included in the study.
  • Habitual use of drugs and/or alcohol within the past six months (Acceptable: Marijuana one time in three months; average of two alcoholic beverages per day; drug and/or alcohol abuse is defined as per the DSM-IV Substance Abuse Criteria)
  • Females who are pregnant or nursing
  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: NCT02056158

Contacts
Contact: Charleen Hollman, PhD, MPA, RN 646-962-2672 chollman@med.cornell.edu
Contact: Marie Guevarra, MS 646-962-4563 mag3007@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College and Weill Cornell Medical Center, Department of Genetic Medicine Recruiting
New York, New York, United States, 10065
Contact: Marie Guevarra, MS    646-962-4563    mag3007@med.cornell.edu   
Contact: Aileen Orpilla, BE    646-962-4564    aio2001@med.cornell.edu   
Sub-Investigator: Steven Gross, Phd         
Sub-Investigator: Robert Kaner, MD         
Sub-Investigator: Jason Mezey, PhD         
Sub-Investigator: Ruba Deeb, PhD         
Sub-Investigator: Matthew Walters, PhD         
Sub-Investigator: Anja Krause, MD         
Sub-Investigator: Marie Guevarra, BS         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: Ronald G Crystal, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT02056158     History of Changes
Other Study ID Numbers: 1307014135
Study First Received: February 4, 2014
Last Updated: January 13, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Weill Medical College of Cornell University:
HIV
COPD
Emphysema
Smoking

ClinicalTrials.gov processed this record on March 26, 2015