Clinical trial NCT01218802: Use of Rosuvastatin in HIV-Infected Subjects to Modulate Cardiovascular Risks
Official title: Randomized Placebo-controlled Trial of Rosuvastatin in HIV-Infected Subjects to Modulate Cardiovascular Risk and Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Heart Disease
Keywords: HIV
Heart Disease
Bone Density
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: AstraZeneca
First posted: 2010-10-11
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Bone Mineral Density (BMD)
timeFrame: 96 weeks
measure: Carotid IMT
timeFrame: 96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Case Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Grace McComsey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.