Ignite Creation Date:
2025-12-25 @ 12:10 AM
Ignite Modification Date:
2026-03-04 @ 1:37 PM
Study NCT ID:
NCT02056158
Status:
COMPLETED
Last Update Posted:
2021-09-22
First Post:
2014-02-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D029424', 'term': 'Pulmonary Disease, Chronic Obstructive'}, {'id': 'D004646', 'term': 'Emphysema'}, {'id': 'D012907', 'term': 'Smoking'}], 'ancestors': [{'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood samples and biopsies from the lower respiratory tract.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 120}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-01-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-09', 'completionDateStruct': {'date': '2015-10-23', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-09-20', 'studyFirstSubmitDate': '2014-02-04', 'studyFirstSubmitQcDate': '2014-02-04', 'lastUpdatePostDateStruct': {'date': '2021-09-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-02-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-10-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes in oxidant stress in the lower respiratory tract in association with HIV infection and smoking', 'timeFrame': 'One year', 'description': 'Using samples obtained from subjects the extent and nature of the HIV/smoking-induced oxidant burden of the lower respiratory tract will be assessed.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['HIV', 'COPD', 'Emphysema', 'Smoking'], 'conditions': ['HIV', 'COPD', 'Emphysema', 'Smoking']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nWe 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.\n\nTo assess this concept, the following aims will be addressed:\n\nSpecific Aim 1 (n=160). To explore the extent of the oxidant stress in the lower respiratory tract in association with HIV infection and smoking.\n\nSpecific Aim 2 (n=160). To evaluate plasma levels of capillary apoptosis and oxidation state of HIV+ nonsmokers and smokers.\n\nSpecific 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'New York Metropolitan area residents', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nHEALTHY VOLUNTEER RESEARCH SUBJECTS\n\n* All study subjects should be able to provide informed consent\n* Males or females ages 18 years and older\n* Must provide HIV informed consent\n\nVOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE\n\n* Must provide informed consent\n* Males and females age 18 years and older\n* 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\n* Must provide HIV informed consent\n\nExclusion Criteria:\n\nHEALTHY VOLUNTEER RESEARCH SUBJECTS\n\n* Individuals not deemed in good overall health by the investigator will not be accepted into the study.\n* 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).\n* 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.\n* Individuals with allergies to atropine or any local anesthetic will not be accepted into the study.\n* Individuals with allergies to pilocarpine, isoproterenol, terbutaline, atropine or aminophylline will not be accepted into the study.\n* Females who are pregnant or nursing will not be accepted into the study\n\nVOLUNTEER RESEARCH SUBJECTS WITH LUNG DISEASE\n\n* 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.\n* 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)\n* Females who are pregnant or nursing'}, 'identificationModule': {'nctId': 'NCT02056158', 'briefTitle': 'HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium', 'organization': {'class': 'OTHER', 'fullName': 'Weill Medical College of Cornell University'}, 'officialTitle': 'HIV+ Alveolar Macrophage Oxidant-mediated Apoptosis of Pulmonary Endothelium', 'orgStudyIdInfo': {'id': '1307014135'}, 'secondaryIdInfos': [{'id': 'U01HL121828', 'link': 'https://reporter.nih.gov/quickSearch/U01HL121828', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'HIV Negative Early COPD Smokers', 'description': 'HIV Negative Early COPD Smokers'}, {'label': 'HIV Negative COPD Smokers', 'description': 'HIV Negative COPD Smokers'}, {'label': 'HIV Negative Nonsmokers', 'description': 'HIV Negative Nonsmokers'}, {'label': 'HIV Negative Smokers', 'description': 'HIV Negative Smokers'}, {'label': 'HIV Positive Smokers', 'description': 'HIV Positive Smokers'}, {'label': 'HIV Positive Nonsmokers', 'description': 'HIV Positive Nonsmokers'}, {'label': 'HIV Positive COPD Smokers', 'description': 'HIV Positive COPD Smokers'}, {'label': 'HIV Positive Early COPD Smokers', 'description': 'HIV Positive Early COPD Smokers'}]}, 'contactsLocationsModule': {'locations': [{'zip': '10021', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Department of Genetic Medicne', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}], 'overallOfficials': [{'name': 'Ronald G Crystal, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Weill Medical College of Cornell University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Weill Medical College of Cornell University', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}