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
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: NCT00663234

  Show 43 Study Locations
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
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014