Blood Markers of Inflammation, Blood Clotting and Blood Vessel Function in HIV-infected Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00776412
First received: October 18, 2008
Last updated: March 14, 2014
Last verified: February 2014
  Purpose

This study will collect information about markers of inflammation, blood clotting and blood vessel function in HIV-infected adults and healthy volunteers. Biomarkers are biological indicators that have been associated with disease. Certain markers of inflammation, blood clotting, and blood vessel function have been associated with risk of cardiovascular disease, stroke and death. One marker, called D-dimer, is a breakdown product of blood clots that has been associated with serious medical conditions, including deep vein thrombosis (formation of a blood clot in a vein deep in the body) and pulmonary embolism (blockage in the pulmonary artery that occurs when a blood clot from a vein breaks away, travels to the pulmonary artery and lodges there). High D-dimer levels have also been associated with cardiovascular disease and stroke risk. In a recent study of HIV-infected patients, higher D-dimer levels were strongly correlated with risk of death from any cause. The significance of changes in D-dimer and other biomarkers in HIV-infected adults is not well understood. This study will further explore D-dimer and other biomarkers to try to better understand the relationships between them and HIV infection.

Healthy volunteers and HIV-infected adults 18 years of age or older may be eligible for this study. Two visits are involved, as follows:

Visit 1 (screening visit to determine eligibility)

  • Medical history and physical examination.
  • Blood tests for HIV infection, blood counts, liver and kidney function.
  • Pregnancy test for women who can become pregnant.

Visit 2

  • Blood tests for hepatitis B and C
  • Blood tests for markers of inflammation and blood clotting.
  • Blood test for genetic changes that influence blood clotting.

In some cases, visits 1 and 2 may be combined.

Optional additional visits (up to 8 visits over 3 years)

  • Additional blood draws for investigation of specific clinical or laboratory findings may be requested.

Condition
Cardiovascular Disease
HIV Infections

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Biomarkers of Inflammation, Coagulation, and Endothelial Function in HIV-Infected Adults

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 375
Study Start Date: October 2008
Detailed Description:

D-dimer, a fibrin degradation product generated as a result of plasmin mediated clot dissolution processes, is an indicator of recent clot formation and subsequent fibrinolysis. Analysis of D-dimer concentration is employed in the diagnosis of deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. More recently, D-dimer levels have been correlated with atherosclerotic cardiovascular disease. In a recent case-control study of biomarkers for cardiovascular disease in human immunodeficiency virus (HIV)-infected adults, baseline D-dimer levels strongly correlated with all-cause mortality. Notably, the association between baseline D-dimer levels and death due to cardiovascular disease was less significant.

At present, the pathophysiology underlying the association of elevated D-dimer concentrations with mortality in HIV is not understood. This study seeks to identify possible mechanisms underlying D-dimer elevations in HIV-infected adults by investigating a number of pathways that may be associated with the elevations using biomarkers of inflammation, hemostasis, thrombosis, platelet function, lipid metabolism, and additional indicators of endothelial function. Further elucidation of plausible pathways contributing to D-dimer elevation could, ultimately, lead to trials of risk-reducing interventions for patients with an elevated D-dimer level.

This study, an exploratory, cross-sectional study of up to 325 subjects, seeks to prospectively collect data on D-dimer and related biomarkers in HIV-infected adults. Initially, the study will recruit HIV-infected adults with HIV viremia who are not taking antiretroviral therapy (ART) and compare their clinical histories and biomarker findings with those from (1) a group of HIV-infected adults with controlled HIV viremia who are receiving ART, and with those from (2) a control group of HIV-negative healthy subjects. Additionally, to study the impact of persistent immune activation and inflammation on immune responses to ART, a cohort of HIV-infected adults with poor CD4+ cell recovery despite effective ART, and to better understand the mechanisms that contribute to impaired immunologic recovery, a cohort of HIV-infected adults with poor CD4+ cell recovery despite effective ART will be enrolled (immunologic non-responder cohort) and for comparison, a control group with similar nadir CD4 counts but with good CD4+ cell recovery on ART.

The study requires 2 visits for screening, history and physical examination, and phlebotomy. A wide array of research assays investigating different aspects of inflammation, coagulation, and endothelial function will be completed. Samples will be stored for future investigation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Age greater than or equal to 18 years
  • Ability to understand and provide informed consent
  • Adequate venous access
  • Adequate blood counts (hemoglobin greater than or equal to 9.0 g/dL, platelets greater than or equal to 50,000 cells/mm(3))
  • Willing and able to comply with study requirements and procedures including storage of blood samples for use in future studies of HIV, AIDS, immune function, inflammation, coagulation, and atherosclerosis
  • Negative serum pregnancy test for females of child-bearing potential (female subjects who have medical documentation of hysterectomy and/or bilateral oophorectomy do not need to undergo pregnancy testing)

For HIV-negative subjects:

- No known history of HIV infection. At enrollment, HIV antibody testing will be performed to confirm negative HIV-1 antibody status.

For HIV-positive subjects:

  • Established HIV diagnosis (previous documentation of HIV-1 infection in the subject s medical record; for subjects without such confirmation, positive ELISA testing confirmed by Western Blot or plasma HIV viral load greater than 10,000 copies/mL)
  • Must be under the care of a physician for HIV and general medical issues.

For HIV-positive subjects enrolling in the immunologic non-responder cohort:

  • CD4 count less than 300 cells/mm(3) after two years of effective combination ART with documentation of viral suppression
  • HIV viral load less than 50 copies/mL at screening, with no viral load greater than 1,000 copies/ml during the period of viral suppression.
  • Not currently receiving any medication known to be associated with a low CD4 count
  • No concurrent illness known to cause a low CD4 count
  • Controls for this cohort will have a historical nadir CD4 count less than 300 cells/mm3, with current CD4 count greater than 300 cells/mm3 after three years of effective combination ART with documentation of viral suppression.

EXCLUSION CRITERIA:

  • Pregnant or breast-feeding
  • Known bleeding or clotting disorder including history of deep vein thrombosis, pulmonary embolism, or hemophilia
  • Current use of warfarin, low molecular weight heparin, clopidogrel or experimental platelet aggregation inhibitor
  • Concurrent malignancy requiring cytotoxic chemotherapy or radiation therapy
  • Substance abuse or severe psychiatric disorder that would interfere with adherence to protocol requirements
  • Any serious medical condition for which the principal investigator feels participation may be contraindicated
  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: NCT00776412

Contacts
Contact: Mary McLaughlin, R.N. (301) 435-8001 mmclaughlin@niaid.nih.gov
Contact: Caryn G Morse, M.D. (301) 496-9320 cmorse@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Caryn G Morse, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00776412     History of Changes
Other Study ID Numbers: 090013, 09-I-0013
Study First Received: October 18, 2008
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cardiovascular Disease
D-dimer
Antiretroviral
Mortality
HIV Positive
HIV Negative
Healthy Volunteer
HV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Immunologic Deficiency Syndromes
Slow Virus Diseases
Cardiovascular Diseases
Inflammation
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 31, 2014