HIV-1 Infection
Conditions
Brief summary
This study is being done with people with HIV infection who have low levels of HDL-C. HDL-C is a type of good cholesterol. People with low HDL-C have a higher risk of heart disease and may have problems with how their blood vessels relax. The endothelium is the inner lining of all blood vessels, such as arteries and veins. When the endothelium is not working properly, the blood vessels have trouble expanding properly, which contributes to the development of heart and blood vessel disease. The main purpose of this study is to see if taking either extended-release niacin or fenofibrate for 24 weeks will help blood vessels work better by improving endothelial function and increasing HDL-C. Niacin and fenofibrate are medications that raise HDL-C. This study will also help determine how safe extended-release niacin and fenofibrate are. The analysis is an as-treated analysis of participants who completed study treatment and had a week 24 BART scan. Safety analyses include all participants
Interventions
DRUGNiacin
Extended-release niacin will be given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24)
DRUGAspirin
Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.
DRUGFenofibrate
Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 infection * Currently on continuous ART for ≥48 weeks. * CD4+ cell count ≥100/mm3 obtained within 60 days prior to study entry. * Most recent HIV-1 RNA below the limit of detection using an ultrasensitive licensed or FDA-approved assay obtained within 60 days prior to study entry. * Certain laboratory values obtained within 60 days prior to study entry (as indicated in the protocol). * HDL-C ≤ 40 mg/dL for men or ≤ 50 mg/dL for women within 60 days prior to study entry by any local assay. * Fasting triglycerides 150-800 mg/dL within 60 days prior to study entry, (initially 200-800 mg/dL, amended during study conduct). * LDL-C \< 160 mg/dL within 60 days prior to study entry. * For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of 15-25 mIU/mL within 60 days prior to entry. * Female subjects of reproductive potential must agree to use a reliable method of contraception while receiving study drug and for 6 weeks after stopping study drug.
Exclusion criteria
* Anticipation of changing ART. * Intent to initiate or change the dose of lipid-lowering drugs or antihypertensives during study. * Active acute infection or other serious illness requiring systemic treatment and/or hospitalization until subject either completes or is clinically stable on therapy in the opinion of the site investigator. * Untreated hypogonadism * History of physician-diagnosed diabetes mellitus or currently taking glucose-lowering medication, (amended during study conduct to allow well-controlled diabetics who are diet controlled or on stable antidiabetic treatment of metformin, sulfonylurea, meglitinides or alpha-glucosidase inhibitors). * Hormonal anabolic therapies within 90 days prior to study entry. * Uncontrolled hypertension within 60 days of study entry. * Acute symptoms of gout within 60 days prior to study entry. * Active peptic ulcer disease as defined by a health care professional. Treatment for gastroesophageal reflux disease (GERD) is not exclusionary. * Documented untreated hypothyroidism per subject's medical records. * Use of thyroid hormone supplements other than for treatment of hypothyroidism within 30 days prior to entry. * Active or symptomatic gallbladder disease within 1 year of study entry. * Active cancer requiring systemic chemotherapy or radiation within 1 year of study entry. * Lipid-lowering agents within 30 days prior to study entry. * Use of fish oil with DHA/EPA \>1000 mg/day within 30 days prior to entry. * Niacin or niacin-containing products that contain \>100 mg daily within 30 days prior to study entry. * Use of vitamin E supplements greater than 200 IU/day within 30 days prior to entry. * Use of vitamin C supplements greater than 250 mg/day within 30 days prior to entry. * Use of systemic cancer chemotherapy, immunomodulators (e.g., growth factors, immune globulin, interleukins, and interferons) within 90 days prior to study entry. * Any systemic glucocorticoid above replacement levels, defined as the equivalent of ≥ 7.5 mg of prednisone daily, within 60 days prior to study entry. * Allergy, sensitivity, or severe intolerance to both aspirin and naproxen (Aleve, Naprosyn). * Symptomatic pancreatitis with hospitalization. * Pregnancy or currently breastfeeding. * Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. * Currently taking or anticipation of starting medication during the study for hepatitis C including interferon and ribavirin. * Documented history of macular edema. * Current severe congestive heart failure (New York Heart Association \[NYHA\] Class III or IV). * History of or current diagnosis of coronary artery disease, angina pectoris, myocardial infarction, previous coronary artery intervention (stenting, angioplasty), peripheral arterial disease (claudication, peripheral arterial angioplasty, or peripheral arterial bypass procedure), cerebrovascular disease (stroke or transient ischemic attack with documented carotid or aortic atherosclerosis), or abdominal aortic aneurysm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Relative FMD (%) | 0 and 24 weeks | The absolute change in maximum relative flow mediated dilation (FMD) (%) of the brachial artery from baseline to week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Triglycerides | 0 and 24 weeks | Change in Triglycerides (mg/dL) from week 0 to week 24. |
| Men: Change in HDL Cholesterol | 0 and 24 weeks | Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24. |
| Women: Change in HDL Cholesterol | 0 and 24 weeks | Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24. |
| Change in HDL Particles | 0 and 24 weeks | Change in total HDL particles from week 0 to week 24 |
| Change in Non-HDL Cholesterol | 0 and 24 weeks | Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24. |
| Change in LDL Cholesterol | 0 and 24 weeks | Change in LDL cholesterol (mg/dL) from week 0 to week 24. |
| Change in Cholesterol | 0 and 24 weeks | Absolute change in total cholesterol from week 0 to week 24. |
| Change in Large HDL Particles | 0 and 24 weeks | Change in Large HDL Particles from week 0 to week 24 |
| Change in HOMA-IR | 0 and 24 weeks | Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR |
| Change in IL-6 | 0 and 24 weeks | Change in IL-6 from week 0 to week 24 |
| Change in C-reactive Protein (CRP) | 0 and 24 weeks | Change in C-reactive protein from week 0 to week 24. |
| Change in D-Dimer | 0 and 24 weeks | Change in D-Dimer from week 0 to week 24 |
| Change in Small LDL Particles | 0 and 24 weeks | Change in Small LDL particles from week 0 to week 24. |
Countries
United States
Participant flow
Recruitment details
A5293 opened to accrual under protocol version 1.0 on November 8, 2011. The first participant was enrolled on January 10, 2012. Accrual to the study closed on April 24, 2013, with a total of 99 participants enrolled from 11 sites within the US.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Extended-release Niacin With Aspirin Niacin: Extended-release niacin given with aspirin 325 mg by mouth in the evening and dose-escalated as follows: 500 mg once daily for 4 weeks, 1000 mg once daily for 4 weeks, then 1500 mg once daily for 16 weeks (through week 24)
Aspirin: Aspirin 325 mg given by mouth in the evening with extended-release niacin through week 24. | 35 |
| Arm B: Fenofibrate Fenofibrate: Fenofibrate administered as 200 mg by mouth once daily for 24 weeks. | 39 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Missed Scan | 2 | 2 |
| Overall Study | Off study Treatment | 9 | 3 |
| Overall Study | Poor scan quality | 3 | 2 |
Baseline characteristics
| Characteristic | Arm A: Extended-release Niacin With Aspirin | Arm B: Fenofibrate | Total |
|---|---|---|---|
| 10 year Coronary Heart Disease (CHD) risk | 3 10yr Framingham CHD risk (%) | 3 10yr Framingham CHD risk (%) | 3 10yr Framingham CHD risk (%) |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 39 Participants | 74 Participants |
| Age, Continuous | 46 years | 45 years | 45 years |
| Baseline Cholesterol | 185 mg/dL | 184 mg/dL | 184 mg/dL |
| C-reactive protein | 1.9 ug/ml | 1.5 ug/ml | 1.7 ug/ml |
| Current Smoker No | 25 participants | 23 participants | 48 participants |
| Current Smoker Yes | 10 participants | 16 participants | 26 participants |
| D-Dimer | 0.30 ug/ml | 0.25 ug/ml | 0.29 ug/ml |
| HDL Particles | 31.8 nmol/L | 30.2 nmol/L | 31.3 nmol/L |
| High Density Lipoprotein (HDL)-Cholesterol Low HDL-C (30-40 mg/dL (Men)/40-50 mg/dL (Women)) | 25 participants | 27 participants | 52 participants |
| High Density Lipoprotein (HDL)-Cholesterol Very low HDL-C (< 30 mg/dL (Men)/< 40 mg/dL (W)) | 10 participants | 12 participants | 22 participants |
| HOMA-IR (Homeostatic model assessment - Insulin Resistance) | 2.5 HOMA IR Score | 3.2 HOMA IR Score | 3.1 HOMA IR Score |
| Interleukin(IL)-6 | 1.1 pg/ml | 1.5 pg/ml | 1.3 pg/ml |
| Large HDL Particles | 2.1 nmol/L | 2.6 nmol/L | 2.5 nmol/L |
| Low Density Lipoprotein (LDL) Cholesterol | 103 mg/dL | 101 mg/dL | 103 mg/dL |
| Men: HDL Cholesterol | 32 mg/dL | 36 mg/dL | 33 mg/dL |
| Non-HDL Cholesterol | 150 mg/dL | 153 mg/dL | 150 mg/dL |
| Race/Ethnicity, Customized American Indian, Alaskan Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black, non-Hispanic | 5 participants | 6 participants | 11 participants |
| Race/Ethnicity, Customized Hispanic, regardless of race | 15 participants | 17 participants | 32 participants |
| Race/Ethnicity, Customized White, non-Hispanic | 15 participants | 15 participants | 30 participants |
| Region of Enrollment United States | 35 participants | 39 participants | 74 participants |
| Relative FMD | 4.38 % | 3.93 % | 4.21 % |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 17 Participants |
| Sex: Female, Male Male | 27 Participants | 30 Participants | 57 Participants |
| Small LDL Particles | 1018 nmol/L | 1052 nmol/L | 1022 nmol/L |
| Triglycerides | 254 mg/dL | 206 mg/dL | 232 mg/dL |
| Women: HDL Cholesterol | 37 mg/dL | 38 mg/dL | 38 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 47 / 50 | 34 / 49 |
| serious Total, serious adverse events | 1 / 50 | 0 / 49 |
Outcome results
Primary
Absolute Change in Relative FMD (%)
The absolute change in maximum relative flow mediated dilation (FMD) (%) of the brachial artery from baseline to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Absolute Change in Relative FMD (%) | 0.60 % FMD |
| Arm B: Fenofibrate | Absolute Change in Relative FMD (%) | 0.50 % FMD |
p-value: 0.28Sign test
p-value: 0.19Sign test
Secondary
Change in Cholesterol
Absolute change in total cholesterol from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan and had lipid panels at weeks 0 and 24.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in Cholesterol | -9 mg/dL |
| Arm B: Fenofibrate | Change in Cholesterol | -2 mg/dL |
Secondary
Change in C-reactive Protein (CRP)
Change in C-reactive protein from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in C-reactive Protein (CRP) | -0.6 ug/ml |
| Arm B: Fenofibrate | Change in C-reactive Protein (CRP) | 0.7 ug/ml |
Secondary
Change in D-Dimer
Change in D-Dimer from week 0 to week 24
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in D-Dimer | 0.06 ug/ml |
| Arm B: Fenofibrate | Change in D-Dimer | 0.06 ug/ml |
Secondary
Change in HDL Particles
Change in total HDL particles from week 0 to week 24
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in HDL Particles | -1.7 nmol/L |
| Arm B: Fenofibrate | Change in HDL Particles | 4.3 nmol/L |
Secondary
Change in HOMA-IR
Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in HOMA-IR | 1.3 HOMA IR Score |
| Arm B: Fenofibrate | Change in HOMA-IR | 0.3 HOMA IR Score |
Secondary
Change in IL-6
Change in IL-6 from week 0 to week 24
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in IL-6 | 0.1 pg/ml |
| Arm B: Fenofibrate | Change in IL-6 | 0.2 pg/ml |
Secondary
Change in Large HDL Particles
Change in Large HDL Particles from week 0 to week 24
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in Large HDL Particles | 0.9 nmol/L |
| Arm B: Fenofibrate | Change in Large HDL Particles | -0.3 nmol/L |
Secondary
Change in LDL Cholesterol
Change in LDL cholesterol (mg/dL) from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in LDL Cholesterol | -1 mg/dL |
| Arm B: Fenofibrate | Change in LDL Cholesterol | 7 mg/dL |
Secondary
Change in Non-HDL Cholesterol
Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in Non-HDL Cholesterol | -17 mg/dL |
| Arm B: Fenofibrate | Change in Non-HDL Cholesterol | -4 mg/dL |
Secondary
Change in Small LDL Particles
Change in Small LDL particles from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in Small LDL Particles | -176 nmol/L |
| Arm B: Fenofibrate | Change in Small LDL Particles | -119 nmol/L |
Secondary
Change in Triglycerides
Change in Triglycerides (mg/dL) from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: This is an as-treated analysis limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Change in Triglycerides | -65 mg/dL |
| Arm B: Fenofibrate | Change in Triglycerides | -54 mg/dL |
Secondary
Men: Change in HDL Cholesterol
Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: Men in the as-treated analysis population, limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Men: Change in HDL Cholesterol | 3 mg/dL |
| Arm B: Fenofibrate | Men: Change in HDL Cholesterol | 6.5 mg/dL |
Secondary
Women: Change in HDL Cholesterol
Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24.
Time frame: 0 and 24 weeks
Population: Women in the as-treated analysis population, limited to 74 participants who had 24 weeks of follow up and a useable week 24 scan.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Extended-release Niacin With Aspirin | Women: Change in HDL Cholesterol | 16 mg/dL |
| Arm B: Fenofibrate | Women: Change in HDL Cholesterol | 8 mg/dL |