Use of Rosuvastatin in HIV-Infected Subjects to Modulate Cardiovascular Risks

NCT ID: NCT01218802

Last Updated: 2016-03-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

147 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2014-05-31

Brief Summary

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The hypothesis of this study is that 96 weeks of Rosuvastatin will be safe and effective in decreasing cardiovascular risk and bone loss in the HIV+ population.

Detailed Description

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While the use of antiretroviral therapy (ART) in recent years has had an impressive impact on mortality and disease progression in HIV-infected patients, nevertheless, cardiovascular disease is a major concern impacting morbidity and mortality in this population.

This study will assess if a potent statin, rosuvastatin, could improve endothelial dysfunction, slow carotid intima media thickness (IMT) progression and bone loss, and decrease inflammation and oxidative stress in HIV-infected ART-treated subjects with good HIV virologic control. The investigators will also see if rosuvastatin will induce beneficial changes in the prevalence of metabolic syndrome and lipid metabolism as well as improve bone turnover markers.

Conditions

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HIV Infections Heart Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Rosuvastatin

Participants will take Rosuvastatin 10 mg. daily for 96 weeks

Group Type ACTIVE_COMPARATOR

Rosuvastatin 10 mg. daily for 96 weeks

Intervention Type DRUG

Participants will take Rosuvastatin 10 mg. daily for 96 weeks.

Sugar Pill placebo

Participants will take a placebo that appears on the exterior to be the same as active drug. They will take one capsule daily.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

participants will take a sugar pill daily for 96 weeks

Interventions

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Rosuvastatin 10 mg. daily for 96 weeks

Participants will take Rosuvastatin 10 mg. daily for 96 weeks.

Intervention Type DRUG

Placebo

participants will take a sugar pill daily for 96 weeks

Intervention Type DRUG

Other Intervention Names

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Crestor

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of HIV Disease
* Age \> 18 years old
* Receiving a stable ARV regimen for at least the last 12 weeks prior to study entry and cumulative duration of ARV for 12 months
* Fasting LDL cholesterol \< 130 mg/dl
* Fasting triglycerides \< 300 mg/dL
* hsCRP \> 2 mg/L or CD38+DR+/CD8+ \> 19%
* If on Vit D replacement therapy, stable regimen for \> 3 months prior to study entry

Exclusion Criteria

* Women who are pregnant or breast feeding
* Any active or chronic inflammatory condition
* Cardiovascular disease
* Current or recent (within 24 weeks of study entry) therapy with omega-3 fatty acids, fibrates, ezetimibe or statins
* Uncontrolled hypothyroidism or hyperthyroidism
* Uncontrolled diabetes
* Use of systemic cancer chemotherapy of immunomodulating agents
* Use of Anabolic agents, growth hormone, growth hormone releasing factor, or any other anabolic agents, except for stable replacement testosterone.
* Use of biphosphonates or other bone therapies
* Any of the following lab findings obtained within 14 days prior to the screening evaluation including the following:

* AST and/or ALT \> 2.5 x ULN
* Hemoglobin \< 9.0 g/dL
* CK \> 3 X ULN
* Calculated creatinine clearance \< 50 mL/min
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Grace McComsey

Chief, Peds ID, Rheumatology and Global Health

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Grace McComsey, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Locations

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University Hospitals of Cleveland Case Medical Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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El Kamari V, Hileman CO, Gholam PM, Kulkarni M, Funderburg N, McComsey GA. Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection. Clin Gastroenterol Hepatol. 2019 Feb;17(3):536-542.e1. doi: 10.1016/j.cgh.2018.05.058. Epub 2018 Jun 14.

Reference Type DERIVED
PMID: 29908359 (View on PubMed)

Dirajlal-Fargo S, Webel AR, Longenecker CT, Kinley B, Labbato D, Sattar A, McComsey GA. The effect of physical activity on cardiometabolic health and inflammation in treated HIV infection. Antivir Ther. 2016;21(3):237-45. doi: 10.3851/IMP2998. Epub 2015 Oct 12.

Reference Type DERIVED
PMID: 26455521 (View on PubMed)

Hale AT, Longenecker CT, Jiang Y, Debanne SM, Labatto DE, Storer N, Hamik A, McComsey GA. HIV vasculopathy: role of mononuclear cell-associated Kruppel-like factors 2 and 4. AIDS. 2015 Aug 24;29(13):1643-50. doi: 10.1097/QAD.0000000000000756.

Reference Type DERIVED
PMID: 26372274 (View on PubMed)

Hileman CO, Dirajlal-Fargo S, Lam SK, Kumar J, Lacher C, Combs GF Jr, McComsey GA. Plasma Selenium Concentrations Are Sufficient and Associated with Protease Inhibitor Use in Treated HIV-Infected Adults. J Nutr. 2015 Oct;145(10):2293-9. doi: 10.3945/jn.115.214577. Epub 2015 Aug 12.

Reference Type DERIVED
PMID: 26269240 (View on PubMed)

Erlandson KM, Jiang Y, Debanne SM, McComsey GA. Rosuvastatin Worsens Insulin Resistance in HIV-Infected Adults on Antiretroviral Therapy. Clin Infect Dis. 2015 Nov 15;61(10):1566-72. doi: 10.1093/cid/civ554. Epub 2015 Jul 8.

Reference Type DERIVED
PMID: 26157049 (View on PubMed)

Lipshultz HM, Hileman CO, Ahuja S, Funderburg NT, McComsey GA. Anaemia is associated with monocyte activation in HIV-infected adults on antiretroviral therapy. Antivir Ther. 2015;20(5):521-7. doi: 10.3851/IMP2940. Epub 2015 Feb 10.

Reference Type DERIVED
PMID: 25668820 (View on PubMed)

Funderburg NT, Jiang Y, Debanne SM, Labbato D, Juchnowski S, Ferrari B, Clagett B, Robinson J, Lederman MM, McComsey GA. Rosuvastatin reduces vascular inflammation and T-cell and monocyte activation in HIV-infected subjects on antiretroviral therapy. J Acquir Immune Defic Syndr. 2015 Apr 1;68(4):396-404. doi: 10.1097/QAI.0000000000000478.

Reference Type DERIVED
PMID: 25514794 (View on PubMed)

Longenecker CT, Hileman CO, Funderburg NT, McComsey GA. Rosuvastatin preserves renal function and lowers cystatin C in HIV-infected subjects on antiretroviral therapy: the SATURN-HIV trial. Clin Infect Dis. 2014 Oct 15;59(8):1148-56. doi: 10.1093/cid/ciu523. Epub 2014 Jul 11.

Reference Type DERIVED
PMID: 25015912 (View on PubMed)

Longenecker CT, Jiang Y, Orringer CE, Gilkeson RC, Debanne S, Funderburg NT, Lederman MM, Storer N, Labbato DE, McComsey GA. Soluble CD14 is independently associated with coronary calcification and extent of subclinical vascular disease in treated HIV infection. AIDS. 2014 Apr 24;28(7):969-77. doi: 10.1097/QAD.0000000000000158.

Reference Type DERIVED
PMID: 24691204 (View on PubMed)

Funderburg NT, Jiang Y, Debanne SM, Storer N, Labbato D, Clagett B, Robinson J, Lederman MM, McComsey GA. Rosuvastatin treatment reduces markers of monocyte activation in HIV-infected subjects on antiretroviral therapy. Clin Infect Dis. 2014 Feb;58(4):588-95. doi: 10.1093/cid/cit748. Epub 2013 Nov 18.

Reference Type DERIVED
PMID: 24253250 (View on PubMed)

Longenecker CT, Funderburg NT, Jiang Y, Debanne S, Storer N, Labbato DE, Lederman MM, McComsey GA. Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med. 2013 Jul;14(6):385-90. doi: 10.1111/hiv.12013. Epub 2013 Jan 18.

Reference Type DERIVED
PMID: 23332012 (View on PubMed)

Other Identifiers

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1R01NR012642-01

Identifier Type: NIH

Identifier Source: org_study_id

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