Safety and Effectiveness of Atorvastatin in HIV Infected Children and Adolescents With Hyperlipidemia - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators:	International Maternal Pediatric Adolescent AIDS Clinical Trials Group Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00663234

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: AIDS Cholesterol

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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:	October 2009
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.
2: Experimental 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.

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

Locations

United States, Colorado
Univ. of Colorado Denver NICHD CRS	Recruiting
Aurora, Colorado, United States, 80045
Contact: Carol Salbenblatt, RN, MS salbenblatt.carol@tchden.org
Principal Investigator: Myron Levin, MD
United States, District of Columbia
Children's National Med. Ctr. Washington DC NICHD CRS	Not yet recruiting
Washington, District of Columbia, United States, 20010
Contact: Romuladus E. Azuine, MPH 202-476-3074 razuine@cnmc.org
Principal Investigator: Steven L. Zeichner, MD, PhD
United States, Florida
Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Not yet recruiting
Miami, Florida, United States, 33136
Contact: Patricia Bryan 305-243-4447 pbryan@med.miami.edu
Principal Investigator: Charles D. Mitchell, MD
South Florida CDC Ft Lauderdale NICHD CRS	Recruiting
Ft Lauderdal, Florida, United States, 33316
Contact: Lisa Bridges, RN 954-728-1125 LBridges@browardhealth.org
United States, Massachusetts
Boston Medical Center Ped. HIV Program NICHD CRS	Recruiting
Boston, Massachusetts, United States, 02118
Contact: Laureen Kay, RN 617-414-3632 laureen.kay@bmc.org
Principal Investigator: Stephen I. Pelton, MD
Children's Hospital of Boston	Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Catherine Kneut, RN, MS, CRNP 617-355-7879 Catherine.kneut@childrens.harvard.edu
United States, New York
Columbia IMPAACT Center	Active, not recruiting
New York, New York, United States, 10032
SUNY Stony Brook NICHD CRS	Not yet recruiting
Stony Brook, New York, United States, 11794
Contact: Denise Ferraro 631-444-8225 denise.ferraro@stonybrook.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Study Chair:	Ann Melvin, MD	Seattle Children's Hospital
Study Chair:	John Farley, MD	University of Maryland at Baltimore

More Information

Additional Information:

Click here for the AIDSinfo Hyperlipidemia Fact Sheet This link exits the ClinicalTrials.gov site

Publications:

Kamin D, Hadigan C. Hyperlipidemia in children with HIV infection: an emerging problem. Expert Rev Cardiovasc Ther. 2003 May;1(1):143-50. Review.

Penzak SR, Chuck SK. Management of protease inhibitor-associated hyperlipidemia. Am J Cardiovasc Drugs. 2002;2(2):91-106.

Solórzano Santos F, Gochicoa Rangel LG, Palacios Saucedo G, Vázquez Rosales G, Miranda Novales MG. Hypertriglyceridemia and hypercholesterolemia in human immunodeficiency virus-1-infected children treated with protease inhibitors. Arch Med Res. 2006 Jan;37(1):129-32.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	IMPAACT P1063, 10167
Study First Received:	April 21, 2008
Last Updated:	January 20, 2010
ClinicalTrials.gov Identifier:	NCT00663234 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Experienced

Additional relevant MeSH terms:

Antimetabolites
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Therapeutic Uses
Retroviridae Infections
Dyslipidemias
RNA Virus Infections
Hyperlipidemias
Metabolic Diseases
Immune System Diseases
Antilipemic Agents

Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
Atorvastatin
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010