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Endothelial Function, Lipoproteins, and Inflammation With Low HDL Cholesterol in HIV: ER Niacin Versus Fenofibrate

Phase 2
Completed
Conditions
HIV-1 Infection
Interventions
Registration Number
NCT01426438
Lead Sponsor
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
99
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm B: FenofibrateFenofibrate-
Arm A: Extended-release niacin with aspirinAspirin-
Arm A: Extended-release niacin with aspirinNiacin-
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
Change in Non-HDL Cholesterol0 and 24 weeks

Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24.

Change in Triglycerides0 and 24 weeks

Change in Triglycerides (mg/dL) from week 0 to week 24.

Women: Change in HDL Cholesterol0 and 24 weeks

Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24.

Change in Small LDL Particles0 and 24 weeks

Change in Small LDL particles from week 0 to week 24.

Change in HOMA-IR0 and 24 weeks

Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR

Change in Cholesterol0 and 24 weeks

Absolute change in total cholesterol from week 0 to week 24.

Men: Change in HDL Cholesterol0 and 24 weeks

Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24.

Change in D-Dimer0 and 24 weeks

Change in D-Dimer from week 0 to week 24

Change in HDL Particles0 and 24 weeks

Change in total HDL particles from week 0 to week 24

Change in LDL Cholesterol0 and 24 weeks

Change in LDL cholesterol (mg/dL) from week 0 to week 24.

Change in IL-60 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 Large HDL Particles0 and 24 weeks

Change in Large HDL Particles from week 0 to week 24

Trial Locations

Locations (14)

University of Colorado Hospital CRS (6101)

🇺🇸

Aurora, Colorado, United States

NY Univ. HIV/AIDS CRS (401)

🇺🇸

New York, New York, United States

University of Southern California (1201)

🇺🇸

Los Angeles, California, United States

UCLA CARE Center CRS (601)

🇺🇸

Los Angeles, California, United States

Harbor-UCLA Med. Ctr. CRS (603)

🇺🇸

Torrance, California, United States

Moses H. Cone Memorial Hospital CRS (3203)

🇺🇸

Greensboro, North Carolina, United States

Case CRS (2501)

🇺🇸

Cleveland, Ohio, United States

University of Washington AIDS CRS (1401)

🇺🇸

Seattle, Washington, United States

Alabama Therapeutics CRS (5801)

🇺🇸

Birmingham, Alabama, United States

New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)

🇺🇸

Newark, New Jersey, United States

Univ. of Cincinnati CRS (2401)

🇺🇸

Cincinnati, Ohio, United States

Duke Univ. Med. Ctr. Adult CRS (1601)

🇺🇸

Durham, North Carolina, United States

Northwestern University CRS (2701)

🇺🇸

Chicago, Illinois, United States

Unc Aids Crs (3201)

🇺🇸

Chapel Hill, North Carolina, United States

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