Translation Evaluation of Aging, Inflammation and HIV in Lung Function (TEAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Cathy Kessinger, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT02154880
First received: April 7, 2014
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

Hypothesis;Aging modifies the risk of pulmonary dysfunction in HIV+ individuals.

The study is a multicenter, prospective observational study of aging and pulmonary function in HIV. We will determine the prevalence and risk factors for lung dysfunction as quantified by pulmonary function testing in both younger (<50 years) and older (≥50 years) HIV+ and HIV-uninfected controls. We will build on existing cohorts and enrich enrollment for individuals over the age of 50 while adjusting for important co-variates such as ART, smoking history, co-infections, and illicit drug use. Evaluations will be scheduled at baseline, 18 months, and 36 months. Study visits will consist of blood draw, questionnaires, and pulmonary function testing.


Condition Intervention
HIV
COPD
Pulmonary Disease
Aging
Procedure: PFT
Procedure: lab work
Procedure: 6MWT
Other: questionnaires

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Translation Evaluation of Aging, Inflammation and HIV in Lung Function

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Number of HIV+ individuals with increased lung dysfunction disproportionate to age. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    determine the prevalence and risk factors for lung dysfunction as quantified by pulmonary function testing in both younger (<50 years) and older (≥50 years) HIV+ and HIV-uninfected controls. We will build on existing cohorts and enrich enrollment for individuals over the age of 50 while adjusting for important co-variates such as ART, smoking history, co-infections, and illicit drug use.

  • Number of HIV COPD patients with increased immune cell and lung cellular aging. [ Time Frame: 3 yrs ] [ Designated as safety issue: No ]
    We will attempt to proved the hypothesis that immune cell and lung cellular aging are increased in HIV COPD.We will examine telomere length and senescence markers in peripheral immune cells, lung immune cells and in lung epithelial cells and will test the hypothesis that HIV+ individuals with worse lung function and faster pulmonary decline manifest a greater degree of immune activation and cellular senescence.

  • Measurement of the inflammome in HIV-associated lung disease. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    We will use this cohort to evaluate biomarkers of inflammation such as IL-6, IL-8, TNF-alpha, and hsCRP to determine if we can identify specific HIV COPD phenotypes using novel decision tree analyses. We will examine relationship of the inflammatory signature associated with COPD to aging markers in Aim 2, as well as ART effects, co-infections, degree of immunosuppression, and other co-variates.


Secondary Outcome Measures:
  • Measurement of Pulmonary immune cell senescence in HIV+ individuals with poor lung function. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    we will test the hypothesis that HIV+ individuals with worse lung function and faster decline manifest a greater degree of pulmonary immune cell senescence and higher levels of senescence-associated cytokines.We will recruit a subset of 30 individuals and perform bronchoscopy with bronchoalveolar lavage (BAL). We will examine telomere length in alveolar macrophages (the primary cell obtained at BAL) and perform flow cytometry for markers of immune activation and senescence as in Aim 2a. We will also measure selected BAL cytokines (Table 2). Bronchoscopies will be performed only at the University of Pittsburgh site due to the need for immediate analyses and cell cultures.

  • The number of lung epithelial cell senescence in HIV+ individuals. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Bronchial epithelial cells are the most easily accessible lung cells, and these cells are likely to be important in the development of HIV COPD. The bronchial epithelium is an active part of the immune response and secretes chemoattractants and pro-inflammatory cytokines as well as matrix metalloproteases that could further perpetuate lung damage. The inflammation, injury, and repair cycle may lead to repeated cell turnover resulting in cellular senescence, apoptosis, and COPD. Lung epithelial cells in HIV- COPD patients display increased senescent markers including decreased telomere length18,19,26-28, but similar changes have not been investigated in HIV COPD. As part of bronchoscopy, we will collect human bronchial epithelial (HBE) cells from endobronchial brushings. Telomere length will be measured in HBE cells. These cells will also be cultured in air-liquid interface (ALI) and we will examine population doubling times, SA-ß-gal, and supernatant cytokines.


Estimated Enrollment: 300
Study Start Date: February 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HIV positive under 50yo
PFT's, lab work, 6MWT, questionnaires, at baseline 18months and 36 months.
Procedure: PFT
Lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder on a NDD EasyOne Pro system before and after bronchodilator administration.
Other Name: Spirometry
Procedure: lab work
The blood will be processed for serum, plasma, and PBMCS, and a portion stored to be used for future use. A hemoglobin and Carboxyhemoglobin will be done in order to calculate the DLCO.
Other Name: blood work
Procedure: 6MWT
The six-minute walk tests are performed in a 100-foot segment of straight hallway marked at 1-foot intervals.
Other Name: six minute walk test
Active Comparator: HIV negative under 50 yo
PFT's, lab work, 6MWT, questionnaires, at baseline 18months and 36 months.
Procedure: PFT
Lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder on a NDD EasyOne Pro system before and after bronchodilator administration.
Other Name: Spirometry
Procedure: lab work
The blood will be processed for serum, plasma, and PBMCS, and a portion stored to be used for future use. A hemoglobin and Carboxyhemoglobin will be done in order to calculate the DLCO.
Other Name: blood work
Procedure: 6MWT
The six-minute walk tests are performed in a 100-foot segment of straight hallway marked at 1-foot intervals.
Other Name: six minute walk test
Other: questionnaires
TEAL, MMRC and ST. George's Questionnaire will be administered. They are paper questionnaires that inquire about respiratory symptoms, quality of life, smoking history and other health issues
Other Name: survey
Active Comparator: HIV positive over 50yo
PFT's, lab work, 6MWT, questionnaires, at baseline 18months and 36 months.
Procedure: PFT
Lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder on a NDD EasyOne Pro system before and after bronchodilator administration.
Other Name: Spirometry
Procedure: lab work
The blood will be processed for serum, plasma, and PBMCS, and a portion stored to be used for future use. A hemoglobin and Carboxyhemoglobin will be done in order to calculate the DLCO.
Other Name: blood work
Procedure: 6MWT
The six-minute walk tests are performed in a 100-foot segment of straight hallway marked at 1-foot intervals.
Other Name: six minute walk test
Other: questionnaires
TEAL, MMRC and ST. George's Questionnaire will be administered. They are paper questionnaires that inquire about respiratory symptoms, quality of life, smoking history and other health issues
Other Name: survey
Active Comparator: HIV negative over 50yo
PFT's, lab work, 6MWT, questionnaires, at baseline 18months and 36 months.
Procedure: PFT
Lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured with the flow-volume loop recorder on a NDD EasyOne Pro system before and after bronchodilator administration.
Other Name: Spirometry
Procedure: lab work
The blood will be processed for serum, plasma, and PBMCS, and a portion stored to be used for future use. A hemoglobin and Carboxyhemoglobin will be done in order to calculate the DLCO.
Other Name: blood work
Procedure: 6MWT
The six-minute walk tests are performed in a 100-foot segment of straight hallway marked at 1-foot intervals.
Other Name: six minute walk test
Other: questionnaires
TEAL, MMRC and ST. George's Questionnaire will be administered. They are paper questionnaires that inquire about respiratory symptoms, quality of life, smoking history and other health issues
Other Name: survey

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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.
  • Uncontrolled hypertension at screening visit (systolic > 160 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.

Exclusion Criteria:

HIV+ young:

  • HIV-1 infection, documented in medical record at any time prior to study entry.
  • Men and women age 45 years and below.
  • Ability and willingness to complete all tests.
  • Participant in MACS, Women's Interagency Health Study and secondarily clinics and the community

HIV+ old:

  • HIV-1 infection, documented in medical record at any time prior to study entry.
  • Men and women age 50 years and above.
  • Ability and willingness to complete all tests.
  • Participant in MACS, Women's Interagency Health Study and secondarily clinics and the community

HIV- young:

  • HIV-uninfected, documented at most recent MACS or WIHS visit.
  • Men and women age 45 years and below.
  • Ability and willingness to complete all tests.
  • Participant in MACS, Women's Interagency Health Study and secondarily clinics and the community

HIV- old:

  • HIV-uninfected, documented at most recent MACS or WIHS visit.
  • Men and women age 50 years and above.
  • Ability and willingness to complete all tests.
  • Participant in MACS, Women's Interagency Health Study and secondarily clinics and the community
  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: NCT02154880

Contacts
Contact: Cathy J Kessinger, RN 412-624-8330
Contact: Dani M Camp, RN 412-624-7403

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kessinger J Cathy, RN    412-624-8330      
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Alison Morris, MD, MS University of Pittsburgh
  More Information

No publications provided

Responsible Party: Cathy Kessinger, RN co investigator, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02154880     History of Changes
Other Study ID Numbers: 13050317, 1R01HL120398-01A0
Study First Received: April 7, 2014
Last Updated: May 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
HIV
lung
aging

Additional relevant MeSH terms:
Lung Diseases
Inflammation
Respiratory Tract Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014