Study of Niacin on Endothelial Function in HIV-infected Subjects With Low High Density Lipoprotein Cholesterol Levels
Information source: University of Hawaii
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Dyslipidemia; Endothelial Dysfunction
Intervention: extended release niacin (Drug)
Phase: N/A
Status: Completed
Sponsored by: University of Hawaii Official(s) and/or principal investigator(s): Dominic C Chow, MD, Principal Investigator, Affiliation: University of Hawaii - Hawaii Center for AIDS
Summary
This study is a pilot study examining the effect of extended-release niacin (Niaspan ®) on
flow-mediated vasodilation (FMD) of the brachial artery, among human immunodeficiency virus
(HIV)-1 infected individuals with low high density lipoprotein (HDL). Brachial artery
diameter will be measured by high-resolution ultrasound at entry and week 12 of study. The
primary comparisons will be change in FMD from baseline to 12 weeks within each of the two
arms. The second specific aim will be to investigate the proportion of the effect of
extended-release niacin on other known cardiovascular markers.
Clinical Details
Official title: Prospective Randomized Pilot Study of the Effect of Niaspan on Endothelial Function in HIV-infected Subjects With Low HDL Cholesterol Levels
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in Flow-mediated Vasodilation (FMD) From Baseline to Study Week 12Flow Mediated Vasodilation
Secondary outcome: High-density Lipoprotein Cholesterol (HDL) Change From Baseline to Study Week 12HDL
Detailed description:
Low high density lipoprotein (HDL) and a lipid pattern consistent with atherogenic
dyslipidemia are also common in the human immunodeficiency virus (HIV)infected population
and is likely due, in large part, to the chronic inflammatory effect of HIV infection per
se. While highly active antiretroviral therapy (HAART) and the resultant reconstitution of
the immune system might be expected to lead to improvement in this lipid profile, studies
from our own research as well as others clearly demonstrate that such therapy fails to fully
correct the low HDL pattern. This coronary artery disease (CAD) risk in the HIV population
is then further compounded by the dyslipidemic effects of various protease inhibitors and
other antiretroviral medications used to treat HIV.
Endothelial dysfunction is an early marker of atherosclerosis that can be determined
non-invasively utilizing assessment of flow-mediated vasodilation (FMD) of the brachial
artery, which may be analogous to blood flow through coronary arteries. Using this novel
technology and HIV as a model of a chronic inflammatory state, we propose to determine if
increasing HDL in subjects with low HDL but no LDL elevation may have potential beneficial
effects. Our overall hypothesis for this pilot project is that increasing HDL levels in
HIV-infected subjects with low HDL by the use of extended-release niacin over a 12 week
period will lead to an identifiable improvement in endothelial function.
Specific Aim 1. To compare endothelial function, measured by flow-mediated vasodilation
(FMD) of the brachial artery, among HIV-1 infected individuals with low high density
lipoprotein (HDL) before and after treatment with extended-release niacin (Niaspan ®)
- Conduct a prospective randomized 12-week clinical trial on HIV-1 infected individuals
with low HDL and normal low density lipoprotein levels who plan to continue their
current anti-retroviral regimens
- Subjects will be randomized to either a treatment or control arm
- Subjects randomized to the treatment arm will receive extended-release niacin (Niaspan
®) starting at 500 mg per night and titrated to a maximum tolerated dose (not exceeding
1500 mg per night)
- Assess changes in FMD of the brachial artery using high-resolution ultrasound from
baseline to week 12 (Total of 2 FMD assessments)
- Correlate changes in HDL with changes in FMD
Hypothesis to be tested:
Use of extended-release niacin will improve FMD among HIV-1 infected individuals with low
HDL
- Following 12 weeks of therapy, subjects treated with extended-release niacin will show
a 8% improvement in FMD compared to controls
- There will be a positive correlation between changes in HDL with changes in FMD
Specific Aim 2. To evaluate changes in lipid parameters, insulin sensitivity and
cardiovascular risk markers with changes in FMD among the treatment and control arms
- Assess and compare changes in non-HDL lipid and lipoprotein parameters with changes in
FMD among the two arms
- Assess and compare changes in insulin sensitivity by homeostasis model assessment
(HOMA) with changes in FMD among the two arms
- Assess and compare changes in cardiovascular risk markers such as adhesion molecules
and C-reactive protein with changes in FMD among the two arms
Hypothesis to be tested:
There will be a correlation between improvements in lipid, insulin sensitivity and
cardiovascular risk markers and FMD in the extended niacin treatment arm
SIGNIFICANCE and RATIONALE: Low HDL cholesterol levels elevate CAD risk independent of low
density lipoprotein (LDL) cholesterol levels. In association with high triglyceride levels
and with small LDL particle size, low HDL is part of the syndrome of atherogenic
dyslipidemia. This form of dyslipidemia is characteristic of the underlying dyslipidemia
found in HIV-infected subjects, likely represents the consequences of chronic inflammatory
changes due to HIV, and contributes substantively to the CAD risk in this population even
without the added risk from dyslipidemic antiretroviral medications. Primary CAD preventive
modalities may be warranted for patients in the HIV population as well as in the general
population who manifest this type of dyslipidemia. Niacin is currently the best medication
available to elevate HDL cholesterol levels. Thus, using the novel technique of assessing
flow-mediated dilatation of the brachial artery, a pilot project is proposed to assess
whether the use of extended release niacin will lead to short term improvement in
endothelial function. If successful, this study may lay the foundation for further studies
into the potential use of niacin for prevention of CAD in patients who are particularly at
risk for CAD due to low HDL cholesterol levels.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age ≥18 years
- Documented HIV infection
- Subjects must have taken HAART 6 months prior to study entry and must be on stable
HAART (no dose change to antiretroviral medications) for at least 30 days immediately
prior to study entry
- HDL < 40 mg/dL • LDL < 130 mg/dL
- All subjects with reproductive potential should utilize adequate contraception for
the duration of this study and for at least 12 weeks following permanent
discontinuation of study treatment. Acceptable methods include male condom, female
condom, diaphragm, or intra-uterine device (IUD)
Exclusion Criteria:
- Known cardiac disease
- Arrhythmia
- History of angina
- Uncontrolled hypertension
- Pregnancy
- Breast-feeding
- Medication known to influence vasodilatation such as nitrates, metformin,
pioglitazone, and rosiglitazone
- Heavy use of vitamin supplements
- Diagnosis of diabetes mellitus
- Treatment with lipid-lowering drugs within 6 weeks prior to study
- Hemoglobin <9. 0 mg/dL
- Absolute neutrophil count <750 cells/mm3
- Platelet count <75,000 platelets/ mm3
- Alanine aminotransferase (ALT or SGOT)/ aspartate aminotransferase (AST or SGPT) /
alkaline phosphatase > 2. 5 x upper limit of normal (ULN)
- Creatinine >1. 5 x ULN
- Individuals with an infection or other medical illness requiring hospitalization
within 14 days prior to study entry
- Individuals who have active alcohol or drug abuse which, in the investigator's
opinion, is sufficient to prevent adequate compliance with study therapy and
evaluations
- Prior history of hypersensitivity reaction to niacin or any other component of the
study drug
Locations and Contacts
University of Hawaii - Hawaii Center for AIDS, Honolulu, Hawaii 96816, United States
Additional Information
Starting date: November 2007
Last updated: November 19, 2012
|