Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects

Study Description

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Brief Summary:

This is a randomised study of the effect of treatment with Combivir (zidovudine [AZT] and lamivudine [3TC]) and Kaletra (lopinavir [LPVr]), alone and in combination, on the development of abnormalities in lipid and glucose metabolism in HIV negative healthy subjects.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Dyslipidemias; Glucose Metabolism Disorders; Metabolic Diseases; Lipodystrophy; Cardiovascular Disease	Drug: Combivir (zidovudine [AZT] / lamivudine [3TC]); Drug: Kaletra (lopinavir [LPVr])	Phase 4

Detailed Description:

Antiretroviral medications, used to treat HIV infection, cause side effects. These include changes in the way that fat is laid down on the body. This results in fat loss from some parts of the body, with fat deposits at other sites, giving a characteristic look known as "HIV associated lipodystrophy" or HIVLD. With these changes, there are also abnormalities in glucose and fat metabolism (collectively termed metabolic abnormalities). In HIV negative populations, these metabolic changes are associated with an increased risk of developing cardiovascular disease (CVD). The aim of this study is to investigate if changes in the body's handling of fats and glucose occur with a short course of treatment in HIV negative subjects and if these correlate to an increased risk of CVD.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	50 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	A 3 Arm, Prospective Study to Compare the Effect of 6 Weeks Exposure to the Combination of Lopinavir (LPVr)/Combivir® (AZT/3TC) Versus Lopinavir Alone or Combivir® Alone in HIV-negative Healthy Subjects on the Development of Abnormalities of Lipid and Glucose Metabolism
Study Start Date :	November 2004
Actual Primary Completion Date :	December 2006
Actual Study Completion Date :	December 2006

Arms and Interventions

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Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. To determine effect of 6 wks ART with LPVr and CBV, alone and in combination, in HIV negative healthy subjects with respect to changes from baseline in genes related to mitochondrial and lipid metabolism in adipocytes

Secondary Outcome Measures :

1. includes: To determine the effect of 6 wks of ART with LPVr and CBV in HIV negative subjects with respect to: changes from baseline in genes related to mitochondrial and lipid and glucose metabolism in monocytes.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Age >18
• Be able to provide written consent to perform in the trial.
• HIV antibody negative and HIV DNA negative at time of entry to the study.

Exclusion Criteria:

• Any history of, or ongoing, mental or physical condition (including suspected or known diagnosis of ischaemic heart disease), which, in the opinion of the investigator, would impede the subject's ability to participate in the trial.
• History of type I or type II diabetes mellitus or previous treatment with antidiabetic medication.
• Prior use of testosterone, oestrogen, growth hormone or other oral glucocorticoid or anabolic steroid products within the previous six months.
• Alcohol or substance abuse which in the opinion of the investigator would affect the subject's ability to participate in the trial.
• Prior use of anti-retroviral agents (including protease inhibitors, nucleoside or non-nucleoside reverse transcriptase inhibitors, investigational antiretroviral agents or fusion inhibitors either in a previous study, as treatment or as part of post-exposure prophylaxis).
• Prior use of any retinoid-containing compound within the previous six months.
• Abnormal coagulation.
• Previous allergic reaction or known allergy to local anaesthetic.
• Previous use of psychotropic medications.
• Concomitant use of medications, including those metabolised by CYP3A4 enzyme system, which, in the opinion of the investigator, would affect the subject's ability to participate in all activities involved in the trial.
• Any grade-three laboratory abnormality recorded from screening bloods.
• Any grade-two laboratory abnormality recorded from screening bloods, which, in the opinion of the investigator, would impede the subject's ability to safely complete all study requirements.
• Gastrointestinal disorders, which may affect drug absorption.
• Any finding on screening clinical examination, which, in the opinion of the investigator, would impede the subject's ability to participate in the rest of the trial.
• Pregnancy
• Evidence of acute or chronic active hepatitis B virus infection by serology performed at baseline.
• Evidence of hepatitis C infection by serology performed at baseline.

Contacts and Locations

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Locations

Australia, New South Wales
St Vincents Hospital
Sydney, New South Wales, Australia, 2010

Sponsors and Collaborators

Kirby Institute

St Vincent's Hospital, Sydney

National Heart, Lung, and Blood Institute (NHLBI)

Garvan Institute of Medical Research

Prince of Wales Hospital, Sydney

Investigators

Principal Investigator:	Andrew D Carr, MD	National Centre in HIV Epidemiology and Clinical Research.
Study Director:	David A Cooper, MD	National Centre in HIV Epidemiology and Clinical Research.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Kirby Institute
ClinicalTrials.gov Identifier:	NCT00192621 History of Changes
Other Study ID Numbers:	SAMA 002 Version 5; ACTR012605000661673
First Posted:	September 19, 2005
Last Update Posted:	April 12, 2012
Last Verified:	April 2012

Keywords provided by Kirby Institute:

HIV negative healthy subjects; Lipid metabolism; Glucose metabolism; Metabolic abnormality	Lipodystrophy; Cardiovascular disease; Treatment Naive; HIV

Additional relevant MeSH terms:

HIV Infections; Cardiovascular Diseases; Congenital Abnormalities; Dyslipidemias; Metabolic Diseases; Lipodystrophy; Glucose Metabolism Disorders; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases	Lipid Metabolism Disorders; Skin Diseases, Metabolic; Skin Diseases; Lamivudine; Zidovudine; Lamivudine, zidovudine drug combination; Lopinavir; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents