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Statin Therapy to Improve Atherosclerosis in HIV Patients

Primary Purpose

Cardiovascular Disease, HIV, Atherosclerosis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

atorvastatin

Placebo

About this trial

This is an interventional treatment trial for Cardiovascular Disease focused on measuring Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, treatment experienced

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Men and women age 18-60 with previously diagnosed HIV disease
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.
Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for >6 months
LDL-cholesterol >70 mg/dL and <130 mg/dL

Exclusion criteria:

History of acute coronary syndrome
Contraindication to statin therapy
Current statin use
AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease
Renal disease or creatinine >1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart)
Infectious illness within past 3 months
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.
Body weight greater than 300 lbs due to CT scanner table limitations
Patients with previous allergic reactions to iodine-containing contrast media
Active illicit drug use
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.
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
Pregnancy or breastfeeding
Coronary artery luminal narrowing >70% seen on coronary CTA

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Atorvastatin

placebo

Arm Description

20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.

Outcomes

Primary Outcome Measures

Coronary and Aortic Plaque Inflammation

12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)

Secondary Outcome Measures

Plaque Progression

12 month percent change in plaque volume

Endothelial Function

Assessment of endothelial function was to be measured by endothelial vasodilator function.

Immune Function

12 month change in CD4 T-lymphocytes

Lipid Profile

12 month change in lipid profile

C-reactive Protein (CRP)

12 month change in Log CRP concentration

Adipocytokines

12 month change in IL-6

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

Full Information

NCT ID

NCT00965185

First Posted

August 24, 2009

Last Updated

November 9, 2017

Sponsor

Massachusetts General Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00965185

Brief Title

Statin Therapy to Improve Atherosclerosis in HIV Patients

Official Title

Statin Therapy to Improve Inflammation and Atherosclerosis in HIV Patients

Study Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Cardiovascular Disease, HIV, Atherosclerosis, Inflammation, Statins, treatment experienced

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Atorvastatin

Arm Type

Experimental

Arm Description

20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.

Arm Title

placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

atorvastatin

Intervention Description

20 mg PO QD for the first 3 months, followed by 40 mg PO QD for the final 9 months.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Coronary and Aortic Plaque Inflammation

Description

12 month change in mean FDG-PET TBR (18-fluorodeoxyglucose positron emission tomography target-to-background ratio)

Time Frame

Measured at baseline and 1 year

Secondary Outcome Measure Information:

Title

Plaque Progression

Description

12 month percent change in plaque volume

Time Frame

Measured at baseline and 1 year

Title

Endothelial Function

Description

Assessment of endothelial function was to be measured by endothelial vasodilator function.

Time Frame

1 year

Title

Immune Function

Description

12 month change in CD4 T-lymphocytes

Time Frame

Measured at baseline and 1 year

Title

Lipid Profile

Description

12 month change in lipid profile

Time Frame

Measured at baseline and 1 year

Title

C-reactive Protein (CRP)

Description

12 month change in Log CRP concentration

Time Frame

Measured at baseline and 1 year

Title

Adipocytokines

Description

12 month change in IL-6

Time Frame

Measured at baseline and 1 year

Title

Liver Function Tests (LFTs)

Description

Time Frame

Measured at baseline, 1, 3, 6, 9, and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Men and women age 18-60 with previously diagnosed HIV disease 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. Stable anti-retroviral (ARV) therapy as defined by no changes in ARV regimen for >6 months LDL-cholesterol >70 mg/dL and <130 mg/dL Exclusion criteria: History of acute coronary syndrome Contraindication to statin therapy Current statin use AST or ALT two times greater than the upper limit of normal or receiving treatment for active liver disease Renal disease or creatinine >1.5 mg/dL (given the risk of contrast nephropathy during CT angiography of the heart) Infectious illness within past 3 months 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. Body weight greater than 300 lbs due to CT scanner table limitations Patients with previous allergic reactions to iodine-containing contrast media Active illicit drug use Patients who report any significant radiation exposure over the course of the year prior to randomization. Significant exposure is defined as: More than 2 percutaneous coronary interventions (PCI) within 12 months of randomization More than 2 myocardial perfusion studies within the past 12 months More than 2 CT angiograms within the past 12 months Any subjects with history of radiation therapy. 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 Pregnancy or breastfeeding Coronary artery luminal narrowing >70% seen on coronary CTA

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven K. Grinspoon, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22820791

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.

Results Reference

background

PubMed Identifier

26424461

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.

Results Reference

result

PubMed Identifier

29419569

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.

Results Reference

derived

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Statin Therapy to Improve Atherosclerosis in HIV Patients

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