Statin Therapy to Improve Atherosclerosis in HIV Patients

HIV Infections Clinical Trial

Official title:

Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00965185
• Other study ID #: 2008-P-000257
• Secondary ID: R01HL095123HL 09
• Status: Completed
• Phase: N/A
• First received: August 24, 2009
• Last updated: November 9, 2017
• Start date: September 2009
• Est. completion date: January 2014

Study information

• Verified date: November 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Disease
• Cardiovascular Diseases
• HIV
• HIV Infections
• Inflammation
• Statins, HMG-CoA

Intervention

Drug:
• atorvastatin
20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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-infec — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Coronary and Aortic Plaque Inflammation	12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)	Measured at baseline and 1 year
Secondary	Plaque Progression	12 month percent change in plaque volume	Measured at baseline and 1 year
Secondary	Endothelial Function	Assessment of endothelial function was to be measured by endothelial vasodilator function.	1 year
Secondary	Immune Function	12 month change in CD4 T-lymphocytes	Measured at baseline and 1 year
Secondary	Lipid Profile	12 month change in lipid profile	Measured at baseline and 1 year
Secondary	C-reactive Protein (CRP)	12 month change in Log CRP concentration	Measured at baseline and 1 year
Secondary	Adipocytokines	12 month change in IL-6	Measured at baseline and 1 year
Secondary	Liver Function Tests (LFTs)	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	Measured at baseline, 1, 3, 6, 9, and 12 months