MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

This is a randomized prospective study into metabolic adverse events during different types of initial antiretroviral therapy in HIV-1-infected men.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; HIV-Associated Lipodystrophy Syndrome
• Intervention / Treatment: Drug: Lopinavir/ritonavir + zidovudine + lamivudine; Drug: Lopinavir/ritonavir + nevirapine

Detailed Description

This is a randomized prospective study into metabolic adverse events during initial antiretroviral therapy in HIV-1-infected men. The following regimens are compared: lopinavir-ritonavir + Combivir and lopinavir-ritonavir + nevirapine (nucleoside reverse transcriptase inhibitor [NRTI]-sparing). Prior to the start of therapy and 3, 12, 24, and 36 months thereafter the distribution of body fat and bone density (bioelectrical impedance analysis [BIA], computed tomography [CT] and dual energy x-ray absorptiometry [DEXA]), lipid spectrum, mitochondrial DNA (peripheral blood mononuclear cells [PBMCs] and adipose tissue biopsies) and vascular measurements are performed. In addition, insulin sensitivity is measured in a subgroup of sixteen individuals by using a hyperinsulinemic euglycemic clamp and performing microvascular measurements. The aim of the study is to obtain prospective insight into the occurrence of various aspects of metabolic adverse events on the one hand and to compare an NRTI-containing therapy with an NRTI-sparing therapy on the other hand. The hypothesis is that in the NRTI-sparing arm, less metabolic and vascular changes are observed than in the NRTI containing regimen.

• Study Type: Interventional
• Enrollment: 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Helsinki University Central Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Amsterdam, Netherlands
    • Medisch Centrum Jan van Goyen
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis, location Oosterpark
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis, location Prinsengracht
  • Amsterdam, Netherlands
    • Slotervaart Ziekenhuis
  • Amsterdam, Netherlands
    • VUMC Free University Medical Center
  • Haarlem, Netherlands
    • Kennemer Gasthuis, location Elisabeth
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum
  • Rotterdam, Netherlands
    • Erasmus Universitair Medisch Centrum
  • den Haag, Netherlands
    • Ziekenhuis Leyenburg
• Spain
  • Barcelona, Spain
    • Hospital Clínic
• United Kingdom
  • London, United Kingdom
    • Royal Free Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male
• Age between 18 and 70 years.
• No prior use of antiretroviral therapy
• Indication for antiretroviral treatment according to common standards

Exclusion Criteria:

• Female sex
• Body mass index (kg/m2) > 35.
• Known history of diabetes mellitus or hyperlipidemia
• Use of coenzyme A reductase inhibitor or fibric acid derivative in the last 6 weeks before inclusion
• Use of the following medication: systemic corticosteroids, thiazide diuretics, calcium-entry blockers, angiotensin-converting inhibitors, nitrates
• Use of nandrolone or testosterone
• Any disorder or condition which can be expected to lead to lessened compliance with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
insulin resistance (3, 12, 24, 36 months)
microvascular function (3, 12, 24, 36 months)
lipid profile (3, 12, 24, 36 months)
body composition (3, 12, 24, 36 months)
macrovascular function (12, 24, 36 months)

Secondary Outcome Measures

Outcome Measure
mitochondrial DNA in PBMC and fatty tissue (12, 24, 36 months)
gene expression, markers of mitochondrial toxicity, inflammation, apoptosis, fat cell differentiation in fatty tissue (12, 24, 36 months)
bone mineral density (12, 24, 36 months)
natural killer cells (3, 12, 24 months)

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Boehringer Ingelheim; Abbott
• Investigators: Principal Investigator: S. A. Danner, MD, PhD, Free University Medical Center; Principal Investigator: P. Reiss, MD, PhD, Academic Medical Center, National AIDS Therapy Evaluation Centre

Publications and helpful links

General Publications

• van Vonderen MG, Blumer RM, Hassink EA, Sutinen J, Ackermans MT, van Agtmael MA, Yki-Jarvinen H, Danner SA, Serlie MJ, Sauerwein HP, Reiss P. Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy. J Acquir Immune Defic Syndr. 2010 Feb;53(2):186-93. doi: 10.1097/QAI.0b013e3181c190f4.
• van Vonderen MG, van Agtmael MA, Hassink EA, Milinkovic A, Brinkman K, Geerlings SE, Ristola M, van Eeden A, Danner SA, Reiss P; MEDICLAS study group. Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss. PLoS One. 2009 May 21;4(5):e5647. doi: 10.1371/journal.pone.0005647.
• van Vonderen MG, Lips P, van Agtmael MA, Hassink EA, Brinkman K, Geerlings SE, Sutinen J, Ristola M, Danner SA, Reiss P. First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir. AIDS. 2009 Jul 17;23(11):1367-76. doi: 10.1097/QAD.0b013e32832c4947.
• van Vonderen MG, Hassink EA, van Agtmael MA, Stehouwer CD, Danner SA, Reiss P, Smulders Y. Increase in carotid artery intima-media thickness and arterial stiffness but improvement in several markers of endothelial function after initiation of antiretroviral therapy. J Infect Dis. 2009 Apr 15;199(8):1186-94. doi: 10.1086/597475.

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Study Completion: July 1, 2008

Study Registration Dates

• First Submitted: July 14, 2005
• First Submitted That Met QC Criteria: July 14, 2005
• First Posted (Estimate): July 21, 2005

Study Record Updates

• Last Update Posted (Estimate): April 25, 2006
• Last Update Submitted That Met QC Criteria: April 24, 2006
• Last Verified: July 1, 2005

More Information

Terms related to this study

• Keywords: HIV; HIV-associated lipodystrophy syndrome
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Lipid Metabolism Disorders; HIV Infections; Skin Diseases, Metabolic; Lipodystrophy; HIV-Associated Lipodystrophy Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Ritonavir; Lopinavir; Lamivudine; Zidovudine
• Other Study ID Numbers: protocol 02-72