Effect of Rosuvastatin on Cardiovascular Risk in HIV-Infected Individuals With Low High Density Lipoprotein (HDL) Cholesterol - Full Text View

Sponsor:	University of Hawaii
Information provided by:	University of Hawaii
ClinicalTrials.gov Identifier:	NCT00986999

Purpose

Rosuvastatin belongs to a class of medications commonly called "statins" which are medications given for high low density lipoprotein (LDL) 'bad' cholesterol to prevent atherosclerosis (hardening of blood vessels) and lower risk of heart attacks and other circulation problems. Recent studies in the general non-HIV infected population have shown that the beneficial effect of statins in preventing circulation problems is larger than would be expected from lowering of LDL-cholesterol alone. It has been suggested that the additional beneficial effect of statins may be due to the anti-inflammatory effect of statins.

The risk of heart attacks and other circulation problems may be high in HIV infected individuals. This may be due to the inflammatory stress effects of HIV. The main purpose of the study is to see if rosuvastatin will have a beneficial effect on the circulatory system in HIV infected individuals even in those who do not have high LDL cholesterol levels. Therefore, in HIV-infected individuals with normal or low LDL cholesterol levels but with evidence of low HDL cholesterol levels which may be a sign of low grade inflammation, the study will look at whether 6 months of rosuvastatin will lead to improvement in brachial artery flow-mediated dilatation (FMD), a marker of early atherosclerosis (hardening of the blood vessels).

Condition	Intervention	Phase
HIV Infections Cardiovascular Disease	Drug: rosuvastatin	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Pilot Study of the Effect of Low-Dose Rosuvastatin on Endothelial Function, Oxidative Stress and Inflammatory Parameters in HIV-Infected Individuals With Low HDL Cholesterol Levels and Low to Normal LDL Cholesterol Levels

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Cholesterol HIV/AIDS Statins

Drug Information available for: Cholest-5-en-3-ol (3beta)- Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

Further study details as provided by University of Hawaii:

Primary Outcome Measures:

Change in flow mediated dilatation (FMD) of the brachial artery [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in HIV biomarkers of immune activation to include CD38 and CD69 expression on T cells and CD16 and CD69 expression on monocytes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in mitochondrial-specific oxidative stress (mt-specific 8-oxo-dG) and oxidative phosphorylation (OXPHOS) protein/enzyme activity [Complex I and Complex IV] levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in glucose homeostasis and insulin resistance as assessed by oral glucose tolerance testing [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in total, trunk, and peripheral fat by dual energy absorptiometry (DXA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in total, HDL and LDL cholesterol and triglyceride levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Change in coronary calcium scores by CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Occurrence of adverse side effects [as assessed by NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Dec. 2004)] [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Change in hsCRP [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	September 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: rosuvastatin rosuvastatin 10 mg qd increased to 20 mg qd as tolerated	Drug: rosuvastatin rosuvastatin 20 mg tablet, 1/2 tab qd increased to a full tablet qd as tolerated x 6 months with optional extension to 2 years Other Name: Crestor
No Intervention: Observation No intervention; patients followed with same assessment as experimental arm

Eligibility

Ages Eligible for Study:	40 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

HIV infection
Age > 40 years old
On stable antiretroviral therapy for > 6 months with no plans to change therapy during the randomized treatment phase of the study
Plasma HIV RNA < 50 copies/mL
Karnofsky performance score > 70 within 30 days prior to study entry
Ability to understand and sign informed consent
Following laboratory values obtained within 30 days prior to randomization:
- Absolute neutrophil count (ANC) > 750/mm3
- Hemoglobin > 8.0 g/dL
- Platelets > 50,000/mm3
- ALT (SGPT) and AST (SGOT) < 2.5 x ULN
- Fasting glucose < 126 mg/dL
- TSH < 3.0 mIU/L
HDL-C < 40 mg/dL in men, < 50 mg/dL in women
Direct LDL-C < 130 mg/dL
Calculated creatinine clearance > 50 mL/min
Willing to be treated with rosuvastatin or be on an observational arm for a minimum of 6 months
Female subject must not participate in a conception process (active attempt to become pregnant) or be post-menopausal. If participating in sexual activity that could lead to pregnancy, the subject must use contraception while receiving study medication and 30 days after stopping the medication

Exclusion criteria

History of past cardiovascular event
Acute illnesses or active AIDS-defining opportunistic infection (OI) within 30 days prior to entry
Other chronic illness including diabetes, autoimmune diseases, and endocrinopathies
Serology positive for hepatitis B surface antigen or hepatitis C antibody
Signs and symptoms of liver failure
Receipt of supraphysiologic glucocorticoid therapy within 3 months prior to study entry
Use of lipid lowering agents within 30 days prior to study entry
Receipt of an HIV vaccine or investigational agents
Pregnancy or breast-feeding
Presence of any active malignancy within the last 5 years
Severe Hypertension (Systolic >/= 180 or Diastolic >/= 110 mm Hg)
Use of oral postmenopausal hormone replacement therapy
Known hypersensitivity to rosuvastatin
Active drug or alcohol dependence
Any acute illness within 30 days prior to study entry that, in the opinion of the site investigator, would interfere with participation in the study.
Use of lopinavir/ritonavir (Kaletra) as part of current HIV antiretroviral regimen

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986999

Contacts

Contact: Lorna Nagamine, RN

808 737-2751 ext 503

Locations

United States, Hawaii
Hawaii Center for AIDS	Recruiting
Honolulu, Hawaii, United States, 96816
Contact: Lorna Nagamine, RN 808-737-2751
Principal Investigator: Cecilia M Shikuma, MD
Sub-Investigator: Todd Seto, M.D.
Sub-Investigator: Dominic Chow, M.D.
Sub-Investigator: Bruce Shiramizu, M.D.
Sub-Investigator: Beau Nakamoto, M.D.
Sub-Investigator: Judy Rudnick, M.D.

Sponsors and Collaborators

University of Hawaii

Investigators

Principal Investigator:

Cecilia Shikuma, MD

Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii

More Information

No publications provided

Responsible Party:	Cecilia M. Shikuma M.D./ Professor of Medicine, John A. Burns School of Medicine, University of Hawaii
ClinicalTrials.gov Identifier:	NCT00986999 History of Changes
Other Study ID Numbers:	H002, R01HL095135
Study First Received:	September 29, 2009
Last Updated:	April 8, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Hawaii:

HIV infected
treatment experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Cardiovascular Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

Slow Virus Diseases
Rosuvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012