Statin Therapy to Improve Atherosclerosis in HIV Patients

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00965185
First received: August 24, 2009
Last updated: February 17, 2015
Last verified: February 2015

August 24, 2009
February 17, 2015
September 2009
January 2014   (final data collection date for primary outcome measure)
Coronary and Aortic Plaque Inflammation [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)
coronary and aortic plaque inflammation [ Time Frame: One year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00965185 on ClinicalTrials.gov Archive Site
  • Plaque Progression [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month percent change in plaque volume
  • Endothelial Function [ Time Frame: Measured at 1 year ] [ Designated as safety issue: No ]
  • Immune Function [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in CD4 T-lymphocytes
  • Lipid Profile [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in lipid profile
  • C-reactive Protein (CRP) [ Time Frame: Measured at baseline and 1 year ] [ Designated as safety issue: No ]
    12 month change in Log CRP concentration
  • Adipocytokines [ Time Frame: Measured at 1 year ] [ Designated as safety issue: No ]
  • Liver Function Tests (LFTs) [ Time Frame: Measured at baseline, 1, 3, 6, 9, and 12 months ] [ Designated as safety issue: Yes ]

    Number of participants with LFT abnormalities (greater than or equal to 3 times the upper limit of normal).

    For reference, the normal ranges for AST and ALT are shown below. Please note that the normal range for ALT at Labcorp changed over the course of the study. AST and ALT elevations were determined based on the normal range at the time the lab test was performed.

    ALT: 0-40 IU/L, 0-44 IU/L, or 0-55 IU/L AST: 0-40 IU/L

  • plaque progression [ Time Frame: one year ] [ Designated as safety issue: No ]
  • endothelial function [ Time Frame: one year ] [ Designated as safety issue: No ]
  • immune function [ Time Frame: one year ] [ Designated as safety issue: No ]
  • lipid profile [ Time Frame: one year ] [ Designated as safety issue: No ]
  • CRP [ Time Frame: one year ] [ Designated as safety issue: No ]
  • adipocytokines [ Time Frame: one year ] [ Designated as safety issue: No ]
  • LFT's [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Statin Therapy to Improve Atherosclerosis in HIV Patients
Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

In HIV patients, statin therapy will attenuate plaque inflammation, thus, making plaques less vulnerable, will deter plaque progression, and improve endothelial function. In addition to known cholesterol-lowering and C-reactive protein lowering effects, immunomodulatory effects of statins will lead to a shift from pro-inflammatory monocyte and T cell subsets to less atherogenic subpopulations.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Cardiovascular Disease
  • HIV
  • Atherosclerosis
  • Inflammation
  • Statins, HMG-CoA
  • HIV Infections
  • Drug: atorvastatin
    20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
  • Drug: Placebo
    Placebo
  • Experimental: Atorvastatin
    20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
    Intervention: Drug: atorvastatin
  • Placebo Comparator: placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
January 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Men and women age 18-60 with previously diagnosed HIV disease
  2. Subclinical coronary artery disease as defined by presence of one or more plaque on coronary CTA without history of cardiac events or cardiac symptoms and no evidence of critical coronary stenosis. Target to background ratio (TBR) as determined by PET of > 1.6.
  3. Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for >6 months
  4. LDL-cholesterol >70 mg/dL and <130 mg/dL

Exclusion criteria:

  1. History of acute coronary syndrome
  2. Contraindication to statin therapy
  3. Current statin use
  4. AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease
  5. Renal disease or creatinine >1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart)
  6. Infectious illness within past 3 months
  7. Contraindication to beta-blocker (including moderate to severe asthma or heart block) or nitroglycerin use as these drugs are given as part of the standard cardiac CT protocol. Previous allergic reaction to beta blocker or nitroglycerin.
  8. Body weight greater than 300 lbs due to CT scanner table limitations
  9. Patients with previous allergic reactions to iodine-containing contrast media
  10. Active illicit drug use
  11. Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as:

    1. More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization
    2. More than 2 myocardial perfusion studies within the past 12 months
    3. More than 2 CT angiograms within the past 12 months
    4. Any subjects with history of radiation therapy.
  12. Patients already scheduled or being considered for a procedure or treatment requiring significant radiation exposure (e.g., radiation therapy, PCI, or catheter ablation of arrhythmia) within 12 months of randomization
  13. Pregnancy or breastfeeding
  14. Coronary artery luminal narrowing >70% seen on coronary CTA
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00965185
2008-P-000257, R01HL095123, HL 095123
Yes
Steven K. Grinspoon, MD, Massachusetts General Hospital
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Steven K. Grinspoon, MD Massachusetts General Hospital
Massachusetts General Hospital
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP