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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01426438
• Other study ID #: ACTG A5293
• Secondary ID: 1U01AI068636
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2011
• Last updated: January 4, 2016
• Start date: November 2011
• Est. completion date: October 2013

Study information

• Verified date: January 2016
• Source: AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 99
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Niacin
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
Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.
• Fenofibrate
Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.

Locations

Country	Name	City	State
United States	University of Colorado Hospital CRS (6101)	Aurora	Colorado
United States	Alabama Therapeutics CRS (5801)	Birmingham	Alabama
United States	Unc Aids Crs (3201)	Chapel Hill	North Carolina
United States	Northwestern University CRS (2701)	Chicago	Illinois
United States	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio
United States	Case CRS (2501)	Cleveland	Ohio
United States	Duke Univ. Med. Ctr. Adult CRS (1601)	Durham	North Carolina
United States	Moses H. Cone Memorial Hospital CRS (3203)	Greensboro	North Carolina
United States	UCLA CARE Center CRS (601)	Los Angeles	California
United States	University of Southern California (1201)	Los Angeles	California
United States	NY Univ. HIV/AIDS CRS (401)	New York	New York
United States	New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)	Newark	New Jersey
United States	University of Washington AIDS CRS (1401)	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS (603)	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
AIDS Clinical Trials Group	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	0 and 24 weeks	No
Secondary	Change in Cholesterol	Absolute change in total cholesterol from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in Triglycerides	Change in Triglycerides (mg/dL) from week 0 to week 24.	0 and 24 weeks	No
Secondary	Men: Change in HDL Cholesterol	Among men, change in HDL Cholesterol (mg/dL) from week 0 to week 24.	0 and 24 weeks	No
Secondary	Women: Change in HDL Cholesterol	Among women, change in HDL cholesterol (mg/dL) from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in HDL Particles	Change in total HDL particles from week 0 to week 24	0 and 24 weeks	No
Secondary	Change in Non-HDL Cholesterol	Change in non-HDL Cholesterol (mg/dL) from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in LDL Cholesterol	Change in LDL cholesterol (mg/dL) from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in Small LDL Particles	Change in Small LDL particles from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in Large HDL Particles	Change in Large HDL Particles from week 0 to week 24	0 and 24 weeks	No
Secondary	Change in HOMA-IR	Absolute change from week 0 to week 24 in insulin resistance as estimated by HOMA-IR	0 and 24 weeks	No
Secondary	Change in IL-6	Change in IL-6 from week 0 to week 24	0 and 24 weeks	No
Secondary	Change in C-reactive Protein (CRP)	Change in C-reactive protein from week 0 to week 24.	0 and 24 weeks	No
Secondary	Change in D-Dimer	Change in D-Dimer from week 0 to week 24	0 and 24 weeks	No