Clinical trial NCT01426438: Endothelial Function, Lipoproteins, and Inflammation With Low HDL Cholesterol in HIV: ER Niacin Versus Fenofibrate
Official title: Effect of HDL-Raising Therapies on Endothelial Function, Lipoproteins, and Inflammation in HIV-infected Subjects With Low HDL Cholesterol: A Phase II Randomized Trial of Extended Release Niacin vs. Fenofibrate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2011-08-31
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Absolute Change in Relative FMD (%)
timeFrame: 0 and 24 weeks
Secondary outcomes:
measure: Change in Cholesterol
timeFrame: 0 and 24 weeks
measure: Change in Triglycerides
timeFrame: 0 and 24 weeks
measure: Men: Change in HDL Cholesterol
timeFrame: 0 and 24 weeks
measure: Women: Change in HDL Cholesterol
timeFrame: 0 and 24 weeks
measure: Change in HDL Particles
timeFrame: 0 and 24 weeks
measure: Change in Non-HDL Cholesterol
timeFrame: 0 and 24 weeks
measure: Change in LDL Cholesterol
timeFrame: 0 and 24 weeks
measure: Change in Small LDL Particles
timeFrame: 0 and 24 weeks
measure: Change in Large HDL Particles
timeFrame: 0 and 24 weeks
measure: Change in HOMA-IR
timeFrame: 0 and 24 weeks
measure: Change in IL-6
timeFrame: 0 and 24 weeks
measure: Change in C-reactive Protein (CRP)
timeFrame: 0 and 24 weeks
measure: Change in D-Dimer
timeFrame: 0 and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS (5801)
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California (1201)
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS (601)
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS (603)
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS (6101)
state: Colorado
city: Chicago
country: United States
facility: Northwestern University CRS (2701)
state: Illinois
city: Newark
country: United States
facility: New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
state: New Jersey
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS (401)
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs (3201)
state: North Carolina
city: Durham
country: United States
facility: Duke Univ. Med. Ctr. Adult CRS (1601)
state: North Carolina
city: Greensboro
country: United States
facility: Moses H. Cone Memorial Hospital CRS (3203)
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS (2401)
state: Ohio
city: Cleveland
country: United States
facility: Case CRS (2501)
state: Ohio
city: Seattle
country: United States
facility: University of Washington AIDS CRS (1401)
state: Washington
Study officials:
affiliation: University of Southern California
name: Michael P Dube, MD
role: STUDY_CHAIR
affiliation: University of Wisconsin School of Medicine and Public Health (Northwestern University CRS)
name: James H Stein, MD
role: STUDY_CHAIR
References:
citation: International Conference on Harmonisation. E2A: Clinical Safety Data Management : Definitions and Standards for Expedited Reporting. Website: http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/clinical-safety-data-management-definitions-and-standards-for-expedited-reporting.html. Accessed May 24, 2011.
citation: Dube MP, Chan ES, Lake JE, Williams B, Kinslow J, Landay A, Coombs RW, Floris-Moore M, Ribaudo HJ, Yarasheski KE. A Randomized, Double-blinded, Placebo-controlled Trial of Sitagliptin for Reducing Inflammation and Immune Activation in Treated and Suppressed Human Immunodeficiency Virus Infection. Clin Infect Dis. 2019 Sep 13;69(7):1165-1172. doi: 10.1093/cid/ciy1051.
citation: Dube MP, Komarow L, Fichtenbaum CJ, Cadden JJ, Overton ET, Hodis HN, Currier JS, Stein JH; AIDS Clinical Trials Group A5293 Study Team. Extended-Release Niacin Versus Fenofibrate in HIV-Infected Participants With Low High-Density Lipoprotein Cholesterol: Effects on Endothelial Function, Lipoproteins, and Inflammation. Clin Infect Dis. 2015 Sep 1;61(5):840-9. doi: 10.1093/cid/civ385. Epub 2015 May 15.