The purpose of this study is to determine the effectiveness of fish oil supplements combined with the drug fenofibrate in treating elevated triglyceride levels in people taking anti-HIV drugs. The participants in this study will have shown no response to fish oil supplements or fenofibrate alone.

Condition	Treatment or Intervention	Phase
HIV Infections Hypertriglyceridemia	Drug: Fenofibrate  Drug: Fish Oil	Phase II

Further Study Details: 

Expected Total Enrollment:  100

Although highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality caused by HIV infection, its use has been associated with lipid abnormalities, particularly elevations in serum triglycerides. Hypertriglyceridemia is a risk factor in the development of cardiovascular and cerebrovascular disease as well as pancreatitis. Lipid-lowering drugs called fibrates have been part of the recommended treatment for elevated triglycerides, but the response to fibrates is incomplete in a large proportion of people. Fish oil capsules containing large amounts of omega-3 fatty acids have been shown to decrease serum triglycerides. However, fish oil supplements or fibrates alone are often inadequate for treating hypertriglyceridemia in people taking HAART. This study will determine whether the combination of the two therapies will lower serum triglycerides in people on HAART more effectively than either therapy alone.

This study comprises two steps. In Step I, participants will be randomly assigned to receive either fish oil supplements or fenofibrate. Participants will be evaluated for treatment response at Week 8. Those who have responded to their treatment will remain on their original single agent therapy through Week 18. Those who have not responded to treatment at Week 10 will move on to Step 2 and begin combination therapy with both fenofibrate and fish oil until Week 18. All participants will return at Week 22 for a follow-up visit. Except at the Week 10 visit, participants will be expected to fast prior to all study visits. Participants will remain on their individual HAART regimens for the duration of the study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• HIV infected
• Fasting LDL <= 160 mg/dL and fasting serum triglycerides >= 400 mg/dL within 28 days prior to study entry
• Willing and able to adhere to a lipid-lowering diet and exercise program for at least 28 days prior to study start and for the duration of the study
• Treatment with HAART for at least 3 months prior to study entry. Participants must be on stable HAART for at least 4 weeks immediately prior to study entry. Participants who have changed from a protease inhibitor (PI)-based regimen to a non-PI-based regimen in the previous 3 months must be on stable HAART for at least 8 weeks immediately prior to study entry.
• Willingness to remain on current HAART regimen for the duration of the study
• Women of reproductive potential must use an acceptable method of contraception while receiving study drugs and for at least 4 weeks after stopping the study drugs
• Men on testosterone replacement therapy must have been on stable therapy for at least 3 months prior to study entry and must be willing to continue stable therapy for the duration of the study
• Participants on hormone replacement therapy other than testosterone replacement therapy and participants using oral contraceptives must have been on stable therapy for at least 28 days prior to study entry and must be willing to continue stable therapy for the duration of the study

Exclusion Criteria:

• Use of investigational antiretroviral drugs within 28 days prior to study entry. Investigational therapies allowed by the study chairs or given in an AACTG study or expanded access trial are permitted, as long as the treatment can be continued for the duration of this study.
• Coronary heart disease
• Atherosclerotic disease risk
• Congestive heart failure
• Uncontrolled hypertension within 28 days prior to study entry
• Active bleeding disorder or active peptic ulcer disease
• Diabetes mellitus that requires pharmacological, dietary control, or diabetic medication within 28 days prior to study entry
• Untreated hypothyroidism. Participants who are currently being treated for hypothyroidism are not excluded if the treatment was initiated at least 28 days prior to study entry.
• Use of levothyroxine or liothyronine, except for treatment of hypothyroidism, within 90 days prior to study entry.
• Active or symptomatic gallbladder disease within 1 year prior to study entry
• Use of systemic cancer chemotherapy within 60 days prior to study entry
• Cancer within 5 years prior to study entry. Skin cancers not requiring systemic treatment are allowed.
• Pregnancy or breast-feeding
• Use of any lipid-lowering agent within 28 days prior to study entry
• Use of hormonal anabolic therapies within 6 months prior to study entry
• Use of systemic steroids
• Use of immune modulators within 28 days prior to study entry
• Use of anticoagulants within 14 days prior to study entry
• Allergy or sensitivity to study drugs or their formulations
• Active drug or alcohol use or dependence that would interfere with adherence to study requirements
• Decreased mental capacity that would interfere with adherence to study requirements
• Active AIDS-defining opportunistic infection (OI) within 28 days prior to study entry. Participants who have no evidence of active disease and are receiving maintenance therapy for AIDS-related OIs will be eligible.
• Any acute illness within 28 days prior to study entry that would interfere with participation in the study

California
      Stanford University, Stanford,  California,  94305-5107,  United States
      San Mateo County AIDS Program, Stanford,  California,  94305-5107,  United States
      Willow Clinic, Stanford,  California,  94305-5107,  United States
      UCLA School of Medicine, Los Angeles,  California,  90095-1793,  United States
      San Francisco General Hospital, San Francisco,  California,  94110,  United States
      University of California, San Diego Antiviral Rese, San Diego,  California,  92103,  United States
Florida
      University of Miami, Miami,  Florida,  33136-1013,  United States
Georgia
      Emory University, Atlanta,  Georgia,  30308,  United States
Hawaii
      University of Hawaii, Honolulu,  Hawaii,  96816-2396,  United States
Illinois
      Cook County Hospital Core Center, Chicago,  Illinois,  60612,  United States
      Northwestern University, Chicago,  Illinois,  60611-3015,  United States
Indiana
      Methodist Hospital of Indiana, Indianapolis,  Indiana,  46202-5250,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242-1201,  United States
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455-0392,  United States
Missouri
      Washington University (St. Louis), St. Louis,  Missouri,  63108-2138,  United States
Nebraska
      Nebraska Health System, Omaha,  Nebraska,  68198-5130,  United States
New York
      Community Health Network, Inc, Rochester,  New York,  14642-0001,  United States
      Beth Israel Medical Center, New York,  New York,  10003,  United States
      University of Rochester Medical Center, Rochester,  New York,  14642-0001,  United States
      Columbia University, New York,  New York,  10032-3784,  United States
      NYU/Bellevue, New York,  New York,  10016-6481,  United States
      McCree McCuller Wellness Center at the Connection, Rochester,  New York,  14642-0001,  United States
North Carolina
      University of North Carolina, Chapel Hill,  North Carolina,  27514,  United States
      The Moses H. Cone Memorial Hospital, Greensboro,  North Carolina,  27401-1004,  United States
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
Ohio
      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States
      Cleveland Clinic, Cleveland,  Ohio,  44106,  United States
      MetroHealth Medical Center, Cleveland,  Ohio,  44109-1998,  United States
      Case Western Reserve University, Cleveland,  Ohio,  44106-5083,  United States
Rhode Island
      Stanley Street Treatment and Resource, Providence,  Rhode Island,  02906,  United States
Tennessee
      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States
Texas
      Dallas VA Medical Center, Dallas,  Texas,  75235-9173,  United States
Washington
      University of Washington (Seattle), Seattle,  Washington,  98104,  United States
Puerto Rico
      University of Puerto Rico, San Juan,  00936-5067,  Puerto Rico

Study chairs or principal investigators

John G. Gerber, MD,  Study Chair,  University of Colorado Health Science Center   

Study ID Numbers:  ACTG A5186
Record last reviewed:  March 2005
Last Updated:  April 7, 2005
Record first received:  January 26, 2004
ClinicalTrials.gov Identifier:  NCT00076518
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08