MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)

Tracking Information
First Submitted Date ICMJE	July 14, 2005
First Posted Date ICMJE	July 21, 2005
Last Update Posted Date	April 25, 2006
Study Start Date ICMJE	January 2003
Primary Completion Date	Not Provided
Current Primary Outcome Measures ICMJE; (submitted: April 24, 2006)	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)
Original Primary Outcome Measures ICMJE; (submitted: July 14, 2005)	insulin resistance (3, 24, 36 months); microvascular function (3, 24, 36 months); lipid profile (3, 24, 36 months); body composition (3, 24, 36 months); macrovascular function (24, 36 months)
Change History	Complete list of historical versions of study NCT00122226 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 24, 2006)	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)
Original Secondary Outcome Measures ICMJE; (submitted: July 14, 2005)	mitochondrial DNA in PBMC and fatty tissue (24, 36 months); apoptosis, gene expression fatty tissue (24, 36 months); bone mineral density (24, 36 months); natural killer cells (3, 12, 24 months)
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
Official Title ICMJE	MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
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.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single; Primary Purpose: Prevention
Condition ICMJE	HIV Infections; HIV-Associated Lipodystrophy Syndrome
Intervention ICMJE	Drug: Lopinavir/ritonavir + zidovudine + lamivudine; Drug: Lopinavir/ritonavir + nevirapine
Study Arms	Not Provided
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Enrollment ICMJE; (submitted: July 14, 2005)	50
Original Enrollment ICMJE	Same as current
Study Completion Date	July 2008
Primary Completion Date	Not Provided
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 70 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Finland, Netherlands, Spain, United Kingdom
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00122226
Other Study ID Numbers ICMJE	protocol 02-72
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor ICMJE	VU University Medical Center
Collaborators ICMJE	Abbott; Boehringer Ingelheim
Investigators ICMJE	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
PRS Account	VU University Medical Center
Verification Date	July 2005
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP