Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia
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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 |
- 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 ]
- 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: | June 2016 |
| Estimated Primary Completion Date: | June 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 |
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
Show 43 Study Locations| 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: | January 10, 2013 |
| 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 March 03, 2013
