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Trial registered on ANZCTR


Registration number
ACTRN12605000661673
Ethics application status
Approved
Date submitted
14/09/2005
Date registered
19/10/2005
Date last updated
19/01/2006
Type of registration
Retrospectively registered

Titles & IDs
Public title
Seronegatives And Metabolic Abnormalities Protocol 2 (SAMA 002)
Scientific title
A three arm, prospective study to compare the effect of six 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.
Universal Trial Number (UTN)
Trial acronym
SAMA 002
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV
796 0
Lipid metabolism 797 0
Glucose metabolism 798 0
Metabolic abnormality 799 0
Lipodystrophy 800 0
Cardiovascular disease 801 0
Condition category
Condition code
Infection 870 870 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Cardiovascular 871 871 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A three arm, prospective study to compare the effect of six 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.
Intervention code [1] 600 0
None
Comparator / control treatment
Control group
Dose comparison

Outcomes
Primary outcome [1] 1120 0
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.
Timepoint [1] 1120 0
Secondary outcome [1] 2065 0
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.
Timepoint [1] 2065 0
Secondary outcome [2] 2066 0
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 adipocyte structure.
Timepoint [2] 2066 0
Secondary outcome [3] 2067 0
To determine 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.
Timepoint [3] 2067 0
Secondary outcome [4] 2068 0
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.
Timepoint [4] 2068 0
Secondary outcome [5] 2069 0
To determine 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.
Timepoint [5] 2069 0
Secondary outcome [6] 2070 0
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.
Timepoint [6] 2070 0
Secondary outcome [7] 2071 0
To assess 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.
Timepoint [7] 2071 0
Secondary outcome [8] 2072 0
To assess the reversibility of any abnormalities developing during the course of the six weeks of dosing, by performing repeat assessments at weeks 12 and 24.
Timepoint [8] 2072 0

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 subjects 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 subjects 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 (appendix C), which, in the opinion of the investigator, would affect the subjects 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 subjects 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 subjects 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.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation sequence was generated centrally and kept at a central location in sealed envelopes grouped according to age of potential study participants.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Sequences were generated centrally to ensure a 2:2:1 randomisation stratified to age group to ensure equal recruitment to each arm across a range of ages. Computer generated randomisation cards, specifying a treatment allocation, were then grouped according to age (age groups a-d) and each individual card placed in an envelope marked with the age group. Envelopes remain at a central location and study staff request a treatment allocation based on potential study subjectâ¿¿s age from administrative staff not directly associated with the study.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2004
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 959 0
Government body
Name [1] 959 0
National Heart Lung and Blood Institute
Country [1] 959 0
United States of America
Funding source category [2] 960 0
Government body
Name [2] 960 0
US National Institutes of Health
Country [2] 960 0
United States of America
Primary sponsor type
University
Name
The University of New South Wales
Address
Country
Australia
Secondary sponsor category [1] 826 0
Hospital
Name [1] 826 0
St Vincents Hospital Sydney Limited
Address [1] 826 0
Country [1] 826 0
Australia
Secondary sponsor category [2] 827 0
Government body
Name [2] 827 0
National Heart Lung and Blood Institute
Address [2] 827 0
Country [2] 827 0
Secondary sponsor category [3] 828 0
Government body
Name [3] 828 0
National Institutes of Health
Address [3] 828 0
Country [3] 828 0
Secondary sponsor category [4] 829 0
Other
Name [4] 829 0
Metabolism and Diabetes Research Group, The Garvan Institute of Medical Research.
Address [4] 829 0
Country [4] 829 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2260 0
St Vincent's Hospital, Sydney Limited
Ethics committee address [1] 2260 0
Ethics committee country [1] 2260 0
Australia
Date submitted for ethics approval [1] 2260 0
Approval date [1] 2260 0
Ethics approval number [1] 2260 0

Summary
Brief summary
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35120 0
Address 35120 0
Country 35120 0
Phone 35120 0
Fax 35120 0
Email 35120 0
Contact person for public queries
Name 9789 0
Patrick WG Mallon
Address 9789 0
The National Centre in HIV Epidemiology and Clinical Research
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 9789 0
Australia
Phone 9789 0
+61 2 83823107
Fax 9789 0
Email 9789 0
[email protected]
Contact person for scientific queries
Name 717 0
Andrew D Carr
Address 717 0
The National Centre in HIV Epidemiology and Clinical Research
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 717 0
Australia
Phone 717 0
+61 2 83823359
Fax 717 0
Email 717 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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