Clinical trial NCT00122226: MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
Official title: MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV Infections
HIV-Associated Lipodystrophy Syndrome
Keywords: HIV
HIV-associated lipodystrophy syndrome
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Abbott
name: Boehringer Ingelheim
First posted: 2005-07-21
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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 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.

Primary outcomes:
measure: insulin resistance (3, 12, 24, 36 months)
measure: microvascular function (3, 12, 24, 36 months)
measure: lipid profile (3, 12, 24, 36 months)
measure: body composition (3, 12, 24, 36 months)
measure: macrovascular function (12, 24, 36 months)
Secondary outcomes:
measure: mitochondrial DNA in PBMC and fatty tissue (12, 24, 36 months)
measure: gene expression, markers of mitochondrial toxicity, inflammation, apoptosis, fat cell differentiation in fatty tissue (12, 24, 36 months)
measure: bone mineral density (12, 24, 36 months)
measure: natural killer cells (3, 12, 24 months)
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Amsterdam
country: Netherlands
facility: Medisch Centrum Jan van Goyen
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis, location Oosterpark
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis, location Prinsengracht
city: Amsterdam
country: Netherlands
facility: Slotervaart ziekenhuis
city: Amsterdam
country: Netherlands
facility: VUMC Free University Medical Center
city: den Haag
country: Netherlands
facility: Ziekenhuis Leyenburg
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis, location Elisabeth
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus Universitair Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Clinic
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Free University Medical Center
name: S. A. Danner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academic Medical Center, National AIDS Therapy Evaluation Centre
name: P. Reiss, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.