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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT01426438
First received: August 30, 2011
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Niacin
Drug: Aspirin
Drug: Fenofibrate
Phase 2

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

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • The absolute change from baseline in % flow mediated dilation (FMD) of the brachial artery after 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute changes from baseline at week 24 in : HDL-C, total cholesterol, non-HDL-C, triglycerides, lipoproteins estimated by NMR Lipoprofile [ Time Frame: Weeks 24 ] [ Designated as safety issue: No ]
  • Absolute changes from baseline in hsCRP, IL-6 D-dimer at week 24 [ Time Frame: Weeks 24 ] [ Designated as safety issue: No ]
  • Absolute changes from baseline in levels of markers of microbial translocation (such as lipopolysaccharide, sCD14, and bacterial 16S rDNA) at week 24 [ Time Frame: Weeks 24 ] [ Designated as safety issue: No ]
  • Absolute change from baseline in insulin resistance as estimated by HOMA-IR at week 24 [ Time Frame: Weeks 24 ] [ Designated as safety issue: No ]
  • Side effects, including flushing and symptoms of myopathy (using a standardized questionnaire), hepatic transaminases [ Time Frame: Weeks 24 ] [ Designated as safety issue: Yes ]
    A list of side effects observed as a result of taking the study treatment.

  • Serious adverse events (SAEs) (defined according to Clinical Safety and Data Management Definitions and Standards for Expedited Reporting [1]) [ Time Frame: Weeks 24 ] [ Designated as safety issue: Yes ]
    A list of adverse events which result in death of the participant or are life threatening. Life threatening refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.


Enrollment: 99
Study Start Date: November 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Extended-release niacin with aspirin 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)
Drug: Aspirin
Aspirin 325 mg will be given by mouth in the evening with extended-release niacin through week 24.
Experimental: Arm B: Fenofibrate Drug: Fenofibrate
Fenofibrate will be administered as 200 mg by mouth once daily for 24 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 200-800 mg/dL within 60 days prior to study entry.
  • 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.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01426438

Locations
United States, Alabama
Alabama Therapeutics CRS (5801)
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS (601)
Los Angeles, California, United States, 90095
University of Southern California (1201)
Los Angeles, California, United States, 90033-1079
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS (6101)
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University CRS (2701)
Chicago, Illinois, United States, 60611
United States, New Jersey
New Jersey Medical School-Adult Clinical Research Ctr. CRS (31477)
Newark, New Jersey, United States, 07103
United States, New York
NY Univ. HIV/AIDS CRS (401)
New York, New York, United States, 10016
United States, North Carolina
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27516
Duke Univ. Med. Ctr. Adult CRS (1601)
Durham, North Carolina, United States, 27710
Moses H. Cone Memorial Hospital CRS (3203)
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
Case CRS (2501)
Cleveland, Ohio, United States, 44106
United States, Washington
University of Washington AIDS CRS (1401)
Seattle, Washington, United States, 98104
Sponsors and Collaborators
AIDS Clinical Trials Group
Investigators
Study Chair: 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)
  More Information

No publications provided

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01426438     History of Changes
Other Study ID Numbers: ACTG A5293, 1U01AI068636
Study First Received: August 30, 2011
Last Updated: July 25, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Aspirin
Niacin
Fenofibrate
Nicotinic Acids
Niacinamide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on September 16, 2014