Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dysbiosis Impact on Lung Disease in HIV (DimPL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04155684
Recruitment Status : Recruiting
First Posted : November 7, 2019
Last Update Posted : October 8, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Alison Morris, University of Pittsburgh

Brief Summary:
Despite the high burden of respiratory symptoms in the HIV+ population, causes of chronic obstructive pulmonary disease (COPD) in individuals with HIV are poorly understood. Microbial communities present in the lungs or gut could play an important role in COPD via their ability to stimulate inflammation and oxidative stress and by the interactions of microbial and host gene transcription. By exploring the impact of the structure and function of microbial communities on the host in HIV-associated COPD, this project could lead to discovery of novel therapeutics to treat and prevent COPD. Subjects will be 20 HIV+ individuals with COPD (FEV1/FVC <0.70 and FEV1 and DLco<80% predicted) and 20 HIV+ individuals with normal lung function (controls) and 10 HIV negative individuals recruited from our ongoing cohorts. Controls will be matched to the individuals with COPD based on age, gender, pack-years of smoking, ART use, HIV viral suppression, and history of illicit drug use. Bronchoscopy will be performed on all subjects. The investigator will uncover mechanisms that contribute to COPD in HIV+ individuals, which will lead to interventional therapies. For example, the investigators evaluate the impact of bacteria on lung epithelial cell gene expression and inflammation and test ability of anti-inflammatories to alter responses. Identification of other key pathways or microbes could also lead to testing of pro-biotics, post-biotics (bacterial metabolites), or therapy with bacteria genetically modified for desired function or metabolites.

Condition or disease
HIV Infections COPD Microbiome

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Dysbiosis Impact on Lung Disease in HIV
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 20, 2021

Resource links provided by the National Library of Medicine


Group/Cohort
HIV + with COPD
COPD will be defined as Subjects with FEV1/FVC<0.70 or FEV1 and DLco < 80% predicted
HIV+ normal
Normal PFT's



Primary Outcome Measures :
  1. Comparison of Ig-bound and BAL bacteria [ Time Frame: 5 years ]
    Using 16S sequencing, we will compare unsorted bacteria from BAL to IgG- and IgM-bound and Ig-negative bacteria in HIV+ individuals with and without COPD.

  2. AEC supernatant cytokines and cell gene expression [ Time Frame: 5 years ]
    Basolateral supernatant cytokines and MMPs will be measured by ELISA, and AEC cytokine and MMP gene expression by rtPCR. We will determine if IgG- or IgM-bound bacteria from HIV+ individuals with COPD generate a greater inflammatory response in co-culture than bacteria from HIV+ individuals without COPD and if this response can be decreased by anti-inflammatories.

  3. AEC function [ Time Frame: 5 years ]
    Trans-epithelial electrical resistance (TEER) will be measured hourly during bacterial co-culture with ALI AECs in the various experimental conditions using an Ag/AgCl electrode106


Biospecimen Retention:   Samples With DNA
Blood, oral samples, bronchial wash and stool will be stored in Dr. Morris's lab at the University of Pittsburgh indefinitely.


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Probability Sample
Study Population
Men and women HIV positive or HIV negative who have participated in The HIV Lung Research group studies in the past.
Criteria

Inclusion Criteria:

  1. HIV-1 infection, documented in medical record at any time prior to study entry.
  2. HIV negative who have prior involvement in an HLRC study.
  3. Men and women age 18 to 80.
  4. Ability and willingness to complete all tests.
  5. Participant in HLRC studies,(PRO10060177, PRO09050521, PRO14070355, PRO08030011, PRO00606151, PRO13050229) MACS(Pitt Men's study), Women's Interagency Health Study, PACT or local HIV + clinics.
  6. COPD will be defined as Subjects with FEV1/FVC<0.70 or FEV1 and DLco < 80% predicted - this is the same criteria for the other HLRC studies listed in #5.

Exclusion Criteria:

  1. 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)
  2. Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
  3. Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4 weeks of study entry.
  4. Acute cardiopulmonary issue in the past 4 months.
  5. 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.
  6. Active cancer requiring systemic chemotherapy or radiation.
  7. Active infection of lungs, brain, or abdomen.
  8. Intravenous drug use or alcohol use that will impair ability to complete study investigations in the opinion of the investigator.
  9. subjects with an upper or lower respiratory tract infection
  10. Individuals with a Primary diagnosis of vocal cord dysfunction, or those with significant or uncontrolled systemic diseases, for example; uncontrolled diabetes or uncontrolled hypertension.
  11. on antibiotics in the past 3 months for an acute infection (prophylaxis OK)
  12. FEV1 less than 30% predicted
  13. Allergy to any drug needed to perform testing and no alternative available (albuterol, atropine, lidocaine, fentanyl, versed, Demerol)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04155684


Contacts
Layout table for location contacts
Contact: Cathy J Kessinger, RN 7247878287 kessingercj@upmc.edu

Locations
Layout table for location information
United States, Pennsylvania
University of Pittsburagh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Cathy J kessinger    412-624-8330    kessingercj@upmc.edu   
Sponsors and Collaborators
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Alison J Morris, MD University of Pittsburgh
Layout table for additonal information
Responsible Party: Alison Morris, Chief, Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04155684    
Other Study ID Numbers: STUDY19060360
R01HL038630-01 ( U.S. NIH Grant/Contract )
First Posted: November 7, 2019    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alison Morris, University of Pittsburgh:
microbiome
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Diseases
Dysbiosis
Respiratory Tract Diseases
Pathologic Processes