MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

• ClinicalTrials.gov Identifier: NCT00122226
• Recruitment Status: Unknown
• First Posted: July 21, 2005
• Last Update Posted: April 25, 2006
• Sponsor: VU University Medical Center
• Collaborators: Abbott; Boehringer Ingelheim
• Information provided by: VU University Medical Center

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
HIV Infections; HIV-Associated Lipodystrophy Syndrome	Drug: Lopinavir/ritonavir + zidovudine + lamivudine; Drug: Lopinavir/ritonavir + nevirapine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single
• Primary Purpose: Prevention
• Official Title: MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
• Study Start Date: January 2003
• Study Completion Date: July 2008

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. insulin resistance (3, 12, 24, 36 months)
2. microvascular function (3, 12, 24, 36 months)
3. lipid profile (3, 12, 24, 36 months)
4. body composition (3, 12, 24, 36 months)
5. macrovascular function (12, 24, 36 months)

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Finland

Helsinki University Central Hospital

Helsinki, Finland

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

Amsterdam, Netherlands

Ziekenhuis Leyenburg

den Haag, Netherlands

Kennemer Gasthuis, location Elisabeth

Haarlem, Netherlands

Leids Universitair Medisch Centrum

Leiden, Netherlands

Erasmus Universitair Medisch Centrum

Rotterdam, Netherlands

Spain

Hospital Clinic

Barcelona, Spain

United Kingdom

Royal Free Hospital

London, United Kingdom

Sponsors and Collaborators

VU University Medical Center

Abbott

Boehringer Ingelheim

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

van Vonderen MG, Blümer 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.

• ClinicalTrials.gov Identifier: NCT00122226
• Other Study ID Numbers: protocol 02-72
• First Posted: July 21, 2005
• Last Update Posted: April 25, 2006
• Last Verified: July 2005

Keywords provided by VU University Medical Center:

HIV; HIV-associated lipodystrophy syndrome

Additional relevant MeSH terms:

HIV-Associated Lipodystrophy Syndrome; Lipodystrophy; HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Skin Diseases, Metabolic; Skin Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Nevirapine; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors