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

NCT01426438 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52931U01AI068636
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 14

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

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (13)

• Change in Cholesterol

  0 and 24 weeks

• Change in Triglycerides

  0 and 24 weeks

• Men: Change in HDL Cholesterol

  0 and 24 weeks

• Women: Change in HDL Cholesterol

  0 and 24 weeks

• Change in HDL Particles

  0 and 24 weeks

Study Arms (2)

Arm A: Extended-release niacin with aspirin

EXPERIMENTAL

Drug: Niacin; Drug: Aspirin

Arm B: Fenofibrate

EXPERIMENTAL

Drug: Fenofibrate

Interventions

Niacin DRUG

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)

Arm A: Extended-release niacin with aspirin

Aspirin DRUG

Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.

Arm A: Extended-release niacin with aspirin

Fenofibrate DRUG

Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.

Arm B: Fenofibrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (14)

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, 35294, United States

Location

University of Southern California (1201)

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS (601)

Los Angeles, California, 90095, United States

Location

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Northwestern University CRS (2701)

Chicago, Illinois, 60611, United States

Location

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

Newark, New Jersey, 07103, United States

Location

NY Univ. HIV/AIDS CRS (401)

New York, New York, 10016, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27516, United States

Location

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

Durham, North Carolina, 27710, United States

Location

Moses H. Cone Memorial Hospital CRS (3203)

Greensboro, North Carolina, 27401, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Related Publications (3)

• 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.

  BACKGROUND

• 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.

  PMID: 30535188 DERIVED

• 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.

  PMID: 25979307 DERIVED

MeSH Terms

Interventions

Niacin; Aspirin; Fenofibrate

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Phenyl Ethers; Ethers; Benzophenones; Ketones

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Michael P Dube, MD

  University of Southern California

  STUDY CHAIR

• James H Stein, MD

  University of Wisconsin School of Medicine and Public Health (Northwestern University CRS)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2011
• First Posted: August 31, 2011
• Study Start: November 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: February 3, 2016
• Results First Posted: October 21, 2014

Record last verified: 2016-01

Locations

US (14)