MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS) - Full Text View

Sponsor:	VU University Medical Center
Collaborators:	Abbott Boehringer Ingelheim Pharmaceuticals
Information provided by:	VU University Medical Center
ClinicalTrials.gov Identifier:	NCT00122226

Purpose

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

Condition	Intervention	Phase
HIV Infections HIV-Associated Lipodystrophy Syndrome	Drug: Lopinavir/ritonavir + zidovudine + lamivudine Drug: Lopinavir/ritonavir + nevirapine	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Single Blind Primary Purpose: Prevention
Official Title:	MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Diabetes Medicines HIV/AIDS

Drug Information available for: Zidovudine Nevirapine Lamivudine Ritonavir Lopinavir

U.S. FDA Resources

Further study details as provided by VU University Medical Center:

Primary Outcome Measures:

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:

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)

Estimated Enrollment:	50
Study Start Date:	January 2003
Estimated Study Completion Date:	July 2008

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00122226

Locations

Finland
Helsinki University Central Hospital
Helsinki, Finland
Netherlands
VUMC Free University Medical Center
Amsterdam, Netherlands
Academic Medical Center
Amsterdam, Netherlands
Onze Lieve Vrouwe Gasthuis, location Oosterpark
Amsterdam, Netherlands
Onze Lieve Vrouwe Gasthuis, location Prinsengracht
Amsterdam, Netherlands
Slotervaart ziekenhuis
Amsterdam, Netherlands
Medisch Centrum Jan van Goyen
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 Pharmaceuticals

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

No publications provided by VU University Medical Center

Additional 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 1;53(2):186-93.

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT00122226 History of Changes
Other Study ID Numbers:	protocol 02-72
Study First Received:	July 14, 2005
Last Updated:	April 24, 2006
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:

HIV
HIV-associated lipodystrophy syndrome

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
HIV-Associated Lipodystrophy Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases

Lipid Metabolism Disorders
Metabolic Diseases
Zidovudine
Nevirapine
Lamivudine
Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on February 09, 2012