Clinical trial NCT00965185: Statin Therapy to Improve Atherosclerosis in HIV Patients
Official title: Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
HIV
Atherosclerosis
Inflammation
Statins, HMG-CoA
HIV Infections
Keywords: Cardiovascular Disease
HIV
Atherosclerosis
Inflammation
Statins
treatment experienced
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-08-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Coronary and Aortic Plaque Inflammation
timeFrame: Measured at baseline and 1 year
Secondary outcomes:
measure: Plaque Progression
timeFrame: Measured at baseline and 1 year
measure: Endothelial Function
timeFrame: 1 year
measure: Immune Function
timeFrame: Measured at baseline and 1 year
measure: Lipid Profile
timeFrame: Measured at baseline and 1 year
measure: C-reactive Protein (CRP)
timeFrame: Measured at baseline and 1 year
measure: Adipocytokines
timeFrame: Measured at baseline and 1 year
measure: Liver Function Tests (LFTs)
timeFrame: Measured at baseline, 1, 3, 6, 9, and 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven K. Grinspoon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012 Jul 25;308(4):379-86. doi: 10.1001/jama.2012.6698.
citation: Lo J, Lu MT, Ihenachor EJ, Wei J, Looby SE, Fitch KV, Oh J, Zimmerman CO, Hwang J, Abbara S, Plutzky J, Robbins G, Tawakol A, Hoffmann U, Grinspoon SK. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2015 Feb;2(2):e52-63. doi: 10.1016/S2352-3018(14)00032-0. Epub 2015 Jan 9.
citation: deFilippi C, Christenson R, Joyce J, Park EA, Wu A, Fitch KV, Looby SE, Lu MT, Hoffmann U, Grinspoon SK, Lo J. Brief Report: Statin Effects on Myocardial Fibrosis Markers in People Living With HIV. J Acquir Immune Defic Syndr. 2018 May 1;78(1):105-110. doi: 10.1097/QAI.0000000000001644.