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

• ClinicalTrials.gov Identifier: NCT00192621
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Last Update Posted: April 12, 2012
• Sponsor: Kirby Institute
• Collaborators: St Vincent's Hospital, Sydney; National Heart, Lung, and Blood Institute (NHLBI); Garvan Institute of Medical Research; Prince of Wales Hospital, Sydney
• Information provided by (Responsible Party): Kirby Institute

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• 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

Outcome Measures

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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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

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

• Responsible Party: Kirby Institute
• ClinicalTrials.gov Identifier: NCT00192621
• 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:

Cardiovascular Diseases; Congenital Abnormalities; Lipodystrophy; Dyslipidemias; Metabolic Diseases; Glucose Metabolism Disorders; 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; Antiviral Agents; Anti-Infective Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; HIV Protease Inhibitors; Viral Protease Inhibitors; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors