Heart Disease, HIV Infections
Conditions
Keywords
HIV, Heart Disease, Bone Density
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.
Interventions
DRUGPlacebo
participants will take a sugar pill daily for 96 weeks
DRUGRosuvastatin 10 mg. daily for 96 weeks
Participants will take Rosuvastatin 10 mg. daily for 96 weeks.
Sponsors
National Institutes of Health (NIH)
AstraZeneca
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density (BMD) | 96 weeks | Measured by change in bone DEXA from baseline to week 96 |
| Carotid IMT | 96 weeks | changes in carotid IMT is a good measure for cardiovascular disease progression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 72 |
| 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 | 75 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Incarcerated | 2 | 0 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Withdrawal by Subject | 3 | 10 |
Baseline characteristics
| Characteristic | Rosuvastatin | Sugar Pill Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 75 Participants | 146 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 9 | 45 years STANDARD_DEVIATION 10 | 45 years STANDARD_DEVIATION 9.8 |
| Mean Absolute CD4 Count | 644 10^6 cells/L STANDARD_DEVIATION 285 | 636 10^6 cells/L STANDARD_DEVIATION 312 | 640 10^6 cells/L STANDARD_DEVIATION 299 |
| Mean ARV Duration | 84 months STANDARD_DEVIATION 63 | 87 months STANDARD_DEVIATION 62 | 86 months STANDARD_DEVIATION 62 |
| Mean HIV Duration | 140 months STANDARD_DEVIATION 79 | 152 months STANDARD_DEVIATION 86 | 146 months STANDARD_DEVIATION 83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 50 Participants | 50 Participants | 100 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 20 Participants | 23 Participants | 43 Participants |
| Region of Enrollment United States | 72 participants | 75 participants | 147 participants |
| Sex: Female, Male Female | 14 Participants | 18 Participants | 32 Participants |
| Sex: Female, Male Male | 58 Participants | 57 Participants | 115 Participants |
| Undetectable Viral Load (<48) | 50 participants | 56 participants | 106 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 72 | 5 / 75 |
| serious Total, serious adverse events | 1 / 72 | 0 / 75 |
Outcome results
Primary
Bone Mineral Density (BMD)
Measured by change in bone DEXA from baseline to week 96
Time frame: 96 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Bone Mineral Density (BMD) | -0.03 percentage of change | Standard Deviation 2.45 |
| Sugar Pill Placebo | Bone Mineral Density (BMD) | -0.53 percentage of change | Standard Deviation 2.7 |
Primary
Carotid IMT
changes in carotid IMT is a good measure for cardiovascular disease progression
Time frame: 96 weeks
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rosuvastatin | Carotid IMT | 1.21 percentage change | Standard Deviation 7.97 |
| Sugar Pill Placebo | Carotid IMT | 4.04 percentage change | Standard Deviation 9.27 |