Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00663234
First received: April 21, 2008
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

Treatment of HIV with antiretroviral regimens that include protease inhibitors (PIs) frequently results in the suppression of HIV viral load, significant immune recovery, and delayed disease progression. However, treatment with PIs has been associated with significant increases in cholesterol and triglycerides in HIV infected adults and children. The purpose of this study is to evaluate the safety and effectiveness of escalating doses of atorvastatin, a FDA-approved drug which lowers cholesterol and triglyceride levels, in HIV infected children receiving antiretroviral regimens containing at least one PI.


Condition Intervention Phase
HIV Infections
Hyperlipidemia
Drug: Atorvastatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Safety and Efficacy Investigation of Atorvastatin for Treatment of PI-Associated Increased LDL Cholesterol in HIV-Infected Children and Adolescents

Resource links provided by NLM:


Further study details as provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Occurence of Grade 3 or 4 toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Low density lipoprotein cholesterol levels [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Atorvastatin pharmacokinetic parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Fasting lipids [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Inflammatory markers for cardiac disease risk [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Viral load [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: August 2009
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants ages 10 to 14 years receiving oral atorvastatin for 48 weeks while on a stable PI-based antiretroviral regimen
Drug: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Other Name: Lipitor
Experimental: 2
Participants ages 15 to 18 years receiving oral atorvastatin for 48 weeks while on a stable PI-based antiretroviral regimen
Drug: Atorvastatin
10 mg to 20 mg atorvastatin taken orally once daily. Dosage is dependent on efficacy criteria.
Other Name: Lipitor

Detailed Description:

Antiretroviral regimens containing PIs often cause hyperlipidemia, which is an increase in the amount of fat (such as cholesterol and triglycerides) in the blood. These increases can lead to heart disease and pancreatitis. Although the mechanism by which PIs cause hyperlipidemia is not clearly understood, there are medications to combat this side effect. The primary purpose of this study is to evaluate the safety and effectiveness of escalating doses of atorvastatin, based on low-density lipoprotein (LDL) cholesterol levels, in HIV-infected children receiving antiretroviral regimens containing at least one PI.

This study will last no longer than 48 weeks. Participants will be assigned to one of two groups according to age. One group will include participants from ages 10 to 14 years with participants from ages 15 to 18 years in the other. The first six participants enrolled in the study will be from the 15 to 18 year old age group. Once safety data through Week 8 on these 6 participants has been analyzed, the remaining participants will be enrolled. All participants will receive atorvastatin in combination with a stable antiretroviral regimen including at least one PI. Each participant will be followed independently according to a dose escalation algorithm for atorvastatin. Participants will begin dosing at 10 mg daily. If efficacy criteria are not met, dosing will increase to no more than 20 mg daily. Atorvastatin will be provided by the study, but antiretrovirals will not.

This study will consist of seven study visits after screening. Visits will occur at study entry and Weeks 4, 8, 12, 24, 36, and 48. A physical exam, medical history, and adherence questionnaire will occur at all study visits. Blood collection will occur at most visits. Urine collection will occur at some visits.

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • CD4 count of at least 15 at screening
  • Viral load of less than 10,000 copies/ml at screening
  • Receiving stable antiretroviral therapy regimen containing at least one protease inhibitor for at least 6 months
  • Tanner stage of 2 or higher
  • Certain fasting LDL cholesterol values and cardiovascular risk factors/co-morbidities. More information on this criterion can be found in the protocol.
  • Able to fast overnight for 8 hours
  • Agree to use two appropriate forms of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Certain abnormal laboratory values
  • Any laboratory or unresolved clinical toxicity equal to Grade 3 or higher
  • Unlikely to remain on current antiretroviral therapy for at least six months after study entry
  • Use of statin, fibrate, or niacin within 3 months prior to study entry
  • Evidence of chronic ongoing myositis or history of myopathy or neuromuscular disorder
  • Symptomatic peripheral neuropathy within 6 months prior to study entry
  • Pharmacologic treatment for depression or other mental disorder excluding Attention Deficit Disorder within 30 days prior to study entry
  • Presence of an active CDC Stage C opportunistic infection or serious bacterial infection requiring therapy within 2 weeks prior to study entry.
  • Chemotherapy for malignancy within 3 months prio to study entry
  • Hepatitis B Surface Antigen positive
  • Hepatitis C viremia
  • Insulin-dependent diabetes mellitus
  • Required treatment with an agent contraindicated with either atorvastatin or PIs. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00663234

  Hide Study Locations
Locations
United States, Alabama
Univ. of Alabama Birmingham NICHD CRS (5096)
Birmingham, Alabama, United States, 35294
United States, California
Miller Children's Hospital Long Beach (5093)
Long Beach, California, United States, 90806
Usc La Nichd Crs (5048)
Los Angeles, California, United States, 90033
UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CR (3601)
Los Angeles, California, United States, 90095
Childrens Hospital Los Angeles NICHD CRS (5090)
Los Angeles, California, United States, 90054
UCSD Mother, Child & Adolescent HIV Program(4601)
San Diego, California, United States, 92103
Univ. of California San Francisco NICHD CRS (5091)
San Francisco, California, United States, 94117
Harbor (UCLA) Medical Center NICHD CRS (5045)
Torrance, California, United States, 90509
United States, Colorado
Univ. of Colorado Denver NICHD CRS (5052)
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Med. Ctr. Washington DC NICHD CRS (5015)
Washington, District of Columbia, United States, 20010
Howard University Washington DC NICHD CRS (5044)
Washington, District of Columbia, United States, 20060
Washington Hospital Center NICHD CRS (5023)
Washington, District of Columbia, United States, 200102931
United States, Florida
South Florida CDC Ft Lauderdale NICHD CRS (5055)
Ft Lauderdal, Florida, United States, 33316
Univ. of Florida Jacksonville NICHD CRS (5051)
Jacksonville, Florida, United States, 32209
Univ. of Miami Ped. Perinatal HIV/AIDS CRS (4201)
Miami, Florida, United States, 33136
University of South Florida Tampa (5018)
Tampa, Florida, United States, 33620
United States, Illinois
Chicago Children's CRS (4001)
Chicago, Illinois, United States, 60614
Rush University Cook County Hospital NICHD CRS (5083)
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane University (5095)
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University NICHD CRS (5092)
Baltimore, Maryland, United States, 21287
University of Maryland NICHD CRS (5094)
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS (5011)
Boston, Massachusetts, United States, 02118
Children's Hospital of Boston NICHD CRS (5009)
Boston, Massachusetts, United States, 02115
WNE Maternal Pediatric Adolescent AIDS CRS (7301)
Worcester, Massachusetts, United States, 01605
United States, Michigan
Wayne State University/Children's Hospital of Michigan NICHD CRS (5041)
Detroit, Michigan, United States, 48201
Hutzel Hospital NICHD CRS (5089)
Detroit, Michigan, United States, 48201-1427
United States, New Jersey
NJ Med School CRS (2802)
Newark, New Jersey, United States, 07103
United States, New York
Bronx-Lebanon Hospital IMPAACT CRS (6901)
Bronx, New York, United States, 10457
Jacobi Medical Center Bronx (5013)
Bronx, New York, United States, 10461
Metropolitan Hospital (5003)
New York, New York, United States, 10029
New York University NY (5012)
New York, New York, United States, 10016
Columbia IMPAACT CRS (4101)
New York, New York, United States, 10032
Strong Memorial Hospital, University of Rochester NICHD CRS (5057)
Rochester, New York, United States, 14642
SUNY Stony Brook NICHD CRS (5040)
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University Medical Center (DUMC) Pediatric CRS (4701)
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Childrens Hospital of Philadelphia (6701)
Philadelphia, Pennsylvania, United States, 19104-4318
United States, Tennessee
St. Jude/UTHSC CRS (6501)
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Hosp. CRS (3801)
Houston, Texas, United States, 77030
United States, Washington
University of Washington NICHD CRS (5029)
Seattle, Washington, United States, 98105
Harborview Medical Center NICHD CRS (5027)
Seattle, Washington, United States, 98105
Univ of Washington Children's Hospital Seattle (5017)
Seattle, Washington, United States, 98105
Puerto Rico
University of Puerto Rico Pediatric HIV/AIDS Research (6601)
San Juan, Puerto Rico, 00936-5067
San Juan City Hosp. PR NICHD CRS (5031)
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
Study Chair: Ann Melvin, MD Seattle Children's Hospital
Study Chair: John Farley, MD University of Maryland at Baltimore
  More Information

Additional Information:
Publications:
Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00663234     History of Changes
Other Study ID Numbers: IMPAACT P1063, U01AI068632, 10167
Study First Received: April 21, 2008
Last Updated: March 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Hyperlipidemias
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014