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

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 19, 2005
• Last Update Posted Date: April 12, 2012
• Study Start Date: November 2004
• Actual Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 8, 2006): 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
• Original Primary Outcome Measures (submitted: September 12, 2005): To determine the effect of six weeks antiretroviral therapy 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.
• Current Secondary Outcome Measures (submitted: June 8, 2006): 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.

Original Secondary Outcome Measures (submitted: September 12, 2005)

• To determine:
• - the effect of six weeks antiretroviral therapy 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 and glucose metabolism in monocytes
• - the effect of six weeks antiretroviral therapy with LPVr and CBV, alone and in combination, in HIV negative healthy subjects with respect to changes from baseline in adipocyte structure.
• - the effect of six weeks LPVr and CBV, alone and in combination, in HIV negative healthy subjects with respect to changes in serum lipids and glucose.
• - the safety of LPVr and CBV, alone and in combination,in HIV negative healthy subjects by evaluating the incidence and severity of adverse events and abnormal laboratory values.
• To compare:
• - the effects of six weeks therapy with LPVr/CBV on the parameters listed above with six weeks of LPVr alone or CBV alone in HIV negative subjects.
• To assess:
• - changes in body composition and plasma concentrations of LPVr over the course of the trial in subjects taking LPVr and CBV, alone and in combination, and compare them to changes in gene expression in monocytes and/or adipose tissue.
• - possible increased risk of cardiovascular disease (CVD) by measurements of changes in brachial artery endothelial reactivity over the course of the trial in individuals taking LPVr and CBV, alone and in combination.
• - the reversibility of any abnormalities developing during the course of the six weeks of dosing, by performing repeat assessments at weeks 12 and 24

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• HIV Infections
• Dyslipidemias
• Glucose Metabolism Disorders
• Metabolic Diseases
• Lipodystrophy
• Cardiovascular Disease

Intervention

• Drug: Combivir (zidovudine [AZT] / lamivudine [3TC])
• Drug: Kaletra (lopinavir [LPVr])

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2005): 50
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2006
• Actual Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT00192621
• Other Study ID Numbers: SAMA 002 Version 5; ACTR012605000661673
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Kirby Institute
• Study 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

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.

• PRS Account: Kirby Institute
• Verification Date: April 2012