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Effect of Tenofovir Disoproxil Fumarate on Lipid Levels in HIV Infected Adults on Stable Anti-HIV Drug Therapy

Primary Purpose

HIV Infections, Dyslipidemia, Hyperlipidemia

Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Tenofovir disoproxil fumarate
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Experienced, TDF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: HIV infected HIV viral load less than 400 copies/ml within 28 days prior to study entry Treatment with stable HAART for at least 90 days prior to study entry. Patients who have taken TDF, didanosine, unboosted atazanavir, or adefovir within 90 days prior to study entry are not eligible. Fasting triglycerides of 150 mg/dl or greater AND less than 1000 mg/dl within 28 days prior to study entry or fasting non-HDL cholesterol 100 mg/dl or greater AND less than 250 mg/dl within 28 days prior to study Hepatitis B virus surface antigen negative within 6 months prior to study entry Have adhered to a lipid-lowering diet and exercise program for at least 28 days prior to study screening, and willing to continue both for the duration of the study Willing to continue any current use of hormone replacement therapy or oral contraceptives for the duration of the study. Participants must have been on a stable dose of these medications for at least 28 days prior to study entry to be eligible. Willing to use acceptable means of contraception Exclusion Criteria: Any lipid-lowering agents within 28 days prior to study entry Nephrotoxins, such as foscarnet and amphotericin B, within 28 days prior to study entry Systemic cancer chemotherapy within 60 days prior to study entry Hormonal anabolic therapies or systemic steroids within 6 months prior to study entry Allergy or sensitivity to the study drug or its formulation Uncontrolled diabetes, as defined by the protocol, within 28 days prior to study entry Current hypothyroidism which has been treated for less than 28 days prior to study entry History of coronary heart disease, known atherosclerotic disease, cerebrovascular disease, peripheral vascular disease, abdominal aortic aneurysm, or arterial blockage Any acute illness within 28 days prior to study entry that, in the opinion of the investigator, may interfere with the study Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study Pregnancy or breastfeeding

Sites / Locations

  • University of Southern California
  • University of California, San Diego Antiviral Research Center
  • University of Colorado Health Sciences Center, Denver
  • University of Miami
  • Indiana University Hospital
  • Methodist Hospital of Indiana
  • Wishard Hospital
  • University of Maryland, Institute of Human Virology
  • Johns Hopkins University
  • Washington University (St. Louis)
  • Beth Israel Medical Center
  • NYU/Bellevue
  • Duke University Medical Center
  • University of Cincinnati
  • Case Western Reserve University
  • MetroHealth Medical Center
  • University of Pennsylvania, Philadelphia
  • University of Pittsburgh
  • University of Texas, Galveston
  • University of Puerto Rico

Outcomes

Primary Outcome Measures

Fasting non-HDL cholesterol at baseline and Weeks 12, 16, and 28

Secondary Outcome Measures

Fasting HDL, total cholesterol, and triglycerides
direct LDL by ultracentrifugation
viral load, CD4 count, and other clinical and laboratory measures

Full Information

First Posted
April 29, 2005
Last Updated
October 26, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00109603
Brief Title
Effect of Tenofovir Disoproxil Fumarate on Lipid Levels in HIV Infected Adults on Stable Anti-HIV Drug Therapy
Official Title
A Pilot Study to Determine the Impact on Dyslipidemia of the Addition of Tenofovir to Stable Background Antiretroviral Therapy in HIV-Infected Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
November 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine the effect of the anti-HIV drug tenofovir disoproxil fumarate (TDF) on lipid levels in HIV infected adults on stable anti-HIV drug therapy. Study hypothesis: The addition of TDF to stable background antiretroviral therapy in HIV infected individuals with dyslipidemia will result in a reduction of non-HDL after 12 weeks of treatment.
Detailed Description
Use of highly active antiretroviral therapy (HAART) has resulted in significant reductions in morbidity and mortality among HIV infected people. However, significant adverse effects, including dyslipidemia, have been associated with HAART. Dyslipidemia may cause elevations in serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations, as well as a decrease in high-density lipoprotein (HDL) concentrations. Dyslipidemia is of particular concern for patients receiving HAART because the condition is associated with increased risk for cardiovascular events. TDF is an antiretroviral that has exhibited favorable lipid effects in several studies in HIV infected people, but the mechanism for the observed lipid-lowering effect of TDF is unknown. This study will evaluate the efficacy of TDF on lowering non-HDL in HIV infected adults currently on stable HAART. HAART itself will not be provided by this study. This study will last 32 weeks. Participants will be randomly assigned to one of two study arms. Arm A participants will receive 12 weeks of TDF daily, 4 weeks of no TDF, 12 weeks of placebo daily, then 4 weeks of no TDF. Arm B participants will receive 12 weeks of placebo daily, 4 weeks of no TDF, 12 weeks of TDF daily, then 4 weeks of no TDF. Participants will continue to take their currently prescribed stable HAART regimen for the duration of the study. There will be 13 study visits over the 32 weeks of the study. Clinical assessments will occur at all visits; blood and urine collection will occur at most visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Dyslipidemia, Hyperlipidemia, Hypercholesterolemia, Hypertriglyceridemia
Keywords
Treatment Experienced, TDF

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Tenofovir disoproxil fumarate
Primary Outcome Measure Information:
Title
Fasting non-HDL cholesterol at baseline and Weeks 12, 16, and 28
Secondary Outcome Measure Information:
Title
Fasting HDL, total cholesterol, and triglycerides
Title
direct LDL by ultracentrifugation
Title
viral load, CD4 count, and other clinical and laboratory measures

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV infected HIV viral load less than 400 copies/ml within 28 days prior to study entry Treatment with stable HAART for at least 90 days prior to study entry. Patients who have taken TDF, didanosine, unboosted atazanavir, or adefovir within 90 days prior to study entry are not eligible. Fasting triglycerides of 150 mg/dl or greater AND less than 1000 mg/dl within 28 days prior to study entry or fasting non-HDL cholesterol 100 mg/dl or greater AND less than 250 mg/dl within 28 days prior to study Hepatitis B virus surface antigen negative within 6 months prior to study entry Have adhered to a lipid-lowering diet and exercise program for at least 28 days prior to study screening, and willing to continue both for the duration of the study Willing to continue any current use of hormone replacement therapy or oral contraceptives for the duration of the study. Participants must have been on a stable dose of these medications for at least 28 days prior to study entry to be eligible. Willing to use acceptable means of contraception Exclusion Criteria: Any lipid-lowering agents within 28 days prior to study entry Nephrotoxins, such as foscarnet and amphotericin B, within 28 days prior to study entry Systemic cancer chemotherapy within 60 days prior to study entry Hormonal anabolic therapies or systemic steroids within 6 months prior to study entry Allergy or sensitivity to the study drug or its formulation Uncontrolled diabetes, as defined by the protocol, within 28 days prior to study entry Current hypothyroidism which has been treated for less than 28 days prior to study entry History of coronary heart disease, known atherosclerotic disease, cerebrovascular disease, peripheral vascular disease, abdominal aortic aneurysm, or arterial blockage Any acute illness within 28 days prior to study entry that, in the opinion of the investigator, may interfere with the study Current drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study Pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Aberg, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Marisa Tungsiripat, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033-1079
Country
United States
Facility Name
University of California, San Diego Antiviral Research Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of Colorado Health Sciences Center, Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262-3706
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136-1013
Country
United States
Facility Name
Indiana University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5250
Country
United States
Facility Name
Methodist Hospital of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5250
Country
United States
Facility Name
Wishard Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Maryland, Institute of Human Virology
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8106
Country
United States
Facility Name
Washington University (St. Louis)
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63108-2138
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
NYU/Bellevue
City
New York
State/Province
New York
ZIP/Postal Code
10016-6481
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0405
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5083
Country
United States
Facility Name
MetroHealth Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109-1998
Country
United States
Facility Name
University of Pennsylvania, Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-2582
Country
United States
Facility Name
University of Texas, Galveston
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0435
Country
United States
Facility Name
University of Puerto Rico
City
San Juan
ZIP/Postal Code
00936-5067
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
PubMed Identifier
12942391
Citation
Dube MP, Stein JH, Aberg JA, Fichtenbaum CJ, Gerber JG, Tashima KT, Henry WK, Currier JS, Sprecher D, Glesby MJ; Adult AIDS Clinical Trials Group Cardiovascular Subcommittee; HIV Medical Association of the Infectious Disease Society of America. Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003 Sep 1;37(5):613-27. doi: 10.1086/378131. Epub 2003 Aug 15. No abstract available.
Results Reference
background
PubMed Identifier
15635112
Citation
Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med. 2005 Jan 6;352(1):48-62. doi: 10.1056/NEJMra041811. No abstract available.
Results Reference
background
PubMed Identifier
15535403
Citation
Martinez E, Tuset M, Milinkovic A, Miro JM, Gatell JM. Management of dyslipidaemia in HIV-infected patients receiving antiretroviral therapy. Antivir Ther. 2004 Oct;9(5):649-63.
Results Reference
background
PubMed Identifier
15765307
Citation
Mehta N, Reilly M. Atherosclerotic cardiovascular disease risk in the HAART-treated HIV-1 population. HIV Clin Trials. 2005 Jan-Feb;6(1):5-24. doi: 10.1310/HT0W-NX2N-U2BM-7LUU.
Results Reference
background
PubMed Identifier
15671795
Citation
Stein JH. Managing cardiovascular risk in patients with HIV infection. J Acquir Immune Defic Syndr. 2005 Feb 1;38(2):115-23. doi: 10.1097/01.qai.0000147525.26746.07.
Results Reference
background
PubMed Identifier
20495438
Citation
Tungsiripat M, Kitch D, Glesby MJ, Gupta SK, Mellors JW, Moran L, Jones L, Alston-Smith B, Rooney JF, Aberg JA. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS. 2010 Jul 17;24(11):1781-4. doi: 10.1097/QAD.0b013e32833ad8b4.
Results Reference
result

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Effect of Tenofovir Disoproxil Fumarate on Lipid Levels in HIV Infected Adults on Stable Anti-HIV Drug Therapy

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