Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients (Quad)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Massachusetts General Hospital
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01766726
First received: January 9, 2013
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

The main aims of this study are to determine whether: a) ART-naïve HIV+ subjects have increased artherosclerotic plaque inflammation/vulnerability, b) newly-initiated QUAD/Stribild therapy will decrease plaque inflammation/vulnerability in these subjects, and c) QUAD/Stribild therapy will improve indices of immune dysregulation and lipid dysfunction as a mechanism of improved plaque inflammation/vulnerability. Parameters of lipid and immune function will also be assessed in healthy control subjects, for comparison.


Condition
HIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effects of Newly-Initiated QUAD Therapy on Aortic/Coronary Inflammation in ART-Naïve Infected Patients

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Degree of aortic/coronary atherosclerotic plaque inflammation assessed via cardiac FDG-PET as target to background ratio (TBR) of the standardized uptake value (SUV).


Secondary Outcome Measures:
  • Aortic/coronary atherosclerotic plaque on coronary computed tomography angiography (coronary CTA) [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Aortic/coronary atherosclerotic plaque assessed via coronary CTA.

  • Lipid and lipoprotein levels [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Levels of lipids and lipoproteins including but not limited to levels of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and levels select apolipoprotein levels.

  • Indices of pro-atherogenic lipid dysfunction [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Including HDL oxidative potential and other assessments of HDL function and structure.

  • Inflammatory biomarker levels [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Levels of inflammatory biomarkers including but not limited to soluble CD163.

  • Percentage of circulating activated leukocyte subsets [ Time Frame: Baseline and change from baseline to 6 months in HIV cohort starting QUAD/Stribild ] [ Designated as safety issue: No ]
    Percentage of circulating activated leukocyte subsets including but not limited to percentage of circulating CD14+CD16+ monocytes assessed via flow cytometry.


Biospecimen Retention:   Samples Without DNA

Plasma, serum.


Estimated Enrollment: 24
Study Start Date: December 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Healthy control subjects
Historical healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to arterial inflammation and coronary atherosclerotic plaque. Prospectively recruited healthy control subjects matched to HIV+ patients on traditional cardiovascular risk factors will be studied at baseline with respect to lipid and immune function.
ART-naïve HIV+ patients starting QUAD/Stribild
ART-naïve HIV+ patients who are about to be started QUAD/Stribild by their treating clinicians will be studied at baseline and 6 months after initiating QUAD/Stribild therapy.

Detailed Description:

Patients with HIV are at higher risk of morbidity and mortality from cardiovascular disease than healthy subjects. Antiretroviral therapy (ART) has greatly increased the lifespan of HIV+ patients, but their risk of CVD remains higher than normal. Previously, it has been shown that compared to healthy control subjects, ART-treated HIV+ patients have more atherosclerotic plaque inflammation in the aorta. This study is intended to determine whether atherosclerotic plaque inflammation/vulnerability is increased in ART-naïve HIV+ patients and whether these parameters can be improved through 6 months of newly-initiated QUAD/Stribild therapy. Additionally, the study will determine whether indices of immune dysregulation and lipid dysfunction are increased in ART-naive HIV+ patients and whether these parameters can also be improved through 6 months of newly initiated QUAD/Stribild therapy.

  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

Subjects with HIV infection being cared for in the Eastern Massachusetts area may be appprised of the study by their treating infectious disease doctors. Additionally, subjects with HIV infection from the community will be recruited via posters, advertisements, e-postings. Healthy control subjects from the community will be recruited via posters, advertisements, and e-postings.

Criteria

HIV-infected Subjects:

Inclusion Criteria:

  • men and women, ages 18+, with documented HIV-infection who are ART-naive and ready to be started on ART with QUAD/Stribild by their treating infectious disease doctors

Exclusion Criteria:

  • history of prior, sustained ART use
  • CD4 <50 or AIDS-defining illness
  • known current opportunistic infection or acute infections (not including Hepatitis B/C)
  • pregnancy or breastfeeding
  • history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease
  • plans for sustained use during 6 month study interval of a confounding immune suppressant medication including intravenous or oral corticosteroid
  • hemoglobin < 12.5 g/dl for men or < 12 g/dl for women
  • eGFR < 70 ml/min/1.73 m2 calculated by CDK-EPI
  • contrast dye allergy
  • contraindication to beta blockers or nitroglycerin administered during MDCT coronary angiography (coronary CTA) protocol
  • body weight > 320 lbs (PET scanner limitation)
  • significant radiation exposure (>2 myocardial perfusion scans or CT angiograms) received within the past year
  • reported active illicit drug use

Healthy control subjects:

Inclusion Criteria:

-men and women, ages 18+, without HIV infection

Exclusion Criteria:

  • known current opportunistic infection or acute infections (not including Hepatitis B/C)
  • pregnancy or breastfeeding
  • history of acute coronary syndrome or coronary artery stenting or surgery, diabetes mellitus, or significant autoimmune/inflammatory disease
  • sustained use of a confounding immune suppressant medication including intravenous or oral corticosteroid
  • hemoglobin < 12.5 g/dl for men or < 12 g/dl for women
  • reported active illicit drug use
  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: NCT01766726

Contacts
Contact: Steven K Grinspoon, MD 617-724-9109 sgrinspoon@partners.org
Contact: Markella V Zanni, MD 617-724-6926 mzanni@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven K Grinspoon, MD    617-724-9109    sgrinspoon@partners.org   
Contact: Markella V Zanni, MD    617-724-6926    mzanni@partners.org   
Sponsors and Collaborators
Massachusetts General Hospital
Gilead Sciences
Investigators
Principal Investigator: Steven K Grinspoon, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Steven K. Grinspoon, MD, Professor of Medicine, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01766726     History of Changes
Other Study ID Numbers: 2012P001138
Study First Received: January 9, 2013
Last Updated: September 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
HIV
Atherosclerosis

Additional relevant MeSH terms:
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on October 23, 2014