Endothelial Function, Lipoproteins, and Inflammation With Low HDL Cholesterol in HIV: ER Niacin Versus Fenofibrate
Condition: HIV-1 Infection
MeSH terms: Inflammation
Intervention: Niacin; Aspirin; Fenofibrate
Intervention description: 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); Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.; Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.
Intervention MeSH terms: Aspirin; Niacin; Fenofibrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 99.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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.