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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| AstraZeneca | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rosuvastatin | Active Comparator | Participants will take Rosuvastatin 10 mg. daily for 96 weeks |
|
| Sugar Pill placebo | Placebo Comparator | Participants will take a placebo that appears on the exterior to be the same as active drug. They will take one capsule daily. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rosuvastatin 10 mg. daily for 96 weeks | Drug | Participants will take Rosuvastatin 10 mg. daily for 96 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Bone Mineral Density (BMD) | Measured by change in bone DEXA from baseline to week 96 | 96 weeks |
| Carotid IMT | changes in carotid IMT is a good measure for cardiovascular disease progression | 96 weeks |
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Inclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Grace McComsey, MD | University Hospitals Cleveland Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals of Cleveland Case Medical Center | Cleveland | Ohio | 44106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29908359 | Derived | 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. | |
| 26455521 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Rosuvastatin | Participants will take Rosuvastatin 10 mg. daily for 96 weeks Rosuvastatin 10 mg. daily for 96 weeks: Participants will take Rosuvastatin 10 mg. daily for 96 weeks. |
| FG001 | 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. Placebo: participants will take a sugar pill daily for 96 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rosuvastatin | Participants will take Rosuvastatin 10 mg. daily for 96 weeks Rosuvastatin 10 mg. daily for 96 weeks: Participants will take Rosuvastatin 10 mg. daily for 96 weeks. |
| BG001 | Sugar Pill Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Bone Mineral Density (BMD) | Measured by change in bone DEXA from baseline to week 96 | The total number of participants who received this outcome who had valid data is less than the total number of enrolled participants, due to drop outs before week 96 and/or invalid testing data from DEXA results. | Posted | Mean | Standard Deviation | percentage of change | 96 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rosuvastatin | Participants will take Rosuvastatin 10 mg. daily for 96 weeks Rosuvastatin 10 mg. daily for 96 weeks: Participants will take Rosuvastatin 10 mg. daily for 96 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Creatinine Kinase | Musculoskeletal and connective tissue disorders | Week 5: Hospitalization secondary to muscle/joint pain; no rhabdomyolysis, no renal compromise. Stopped study drug but remained on study for follow-up. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Blood Pressure | Cardiac disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Grace McComsey, MD | Case Western Reserve University | 2168442739 | gam9@case.edu |
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D006331 | Heart Diseases |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
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| Placebo | Drug | participants will take a sugar pill daily for 96 weeks |
|
| 26372274 | Derived | 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. |
| 26269240 | Derived | 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. |
| 26157049 | Derived | 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. |
| 25668820 | Derived | 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. |
| 25514794 | Derived | 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. |
| 25015912 | Derived | 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. |
| 24691204 | Derived | 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. |
| 24253250 | Derived | 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. |
| 23332012 | Derived | 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. |
| Adverse Event |
|
| Incarcerated |
|
Participants will take a placebo that appears on the exterior to be the same as active drug. They will take one capsule daily.
Placebo: participants will take a sugar pill daily for 96 weeks
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mean HIV Duration | Mean | Standard Deviation | months |
|
| Mean ARV Duration | Mean | Standard Deviation | months |
|
| Undetectable Viral Load (<48) | Number | participants |
|
| Mean Absolute CD4 Count | Mean | Standard Deviation | 10^6 cells/L |
|
|
|
| Primary | Carotid IMT | changes in carotid IMT is a good measure for cardiovascular disease progression | The number of participants who received a final CIMT is less than the number of participants enrolled, due in part to study drop outs and/or invalid data measures. | Posted | Mean | Standard Deviation | percentage change | 96 weeks |
|
|
|
| 1 |
| 72 |
| 5 |
| 72 |
| EG001 | 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. Placebo: participants will take a sugar pill daily for 96 weeks | 0 | 75 | 5 | 75 |
|
| Muscle, Joint Pain | Musculoskeletal and connective tissue disorders | 2 subjects on placebo reported this AE; no subjects on active drug reported this. |
|
| Elevated Glucose | Endocrine disorders |
|
| Elevated Creatinine | Renal and urinary disorders |
|
| Elevated liver enzymes | Hepatobiliary disorders |
|
| Elevated Creatinine Kinase | Musculoskeletal and connective tissue disorders |
|
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| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D002318 | Cardiovascular Diseases |
| D006845 |
| Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |