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: Amsterdam UMC, location VUmc
• Collaborators: Abbott; Boehringer Ingelheim
• Information provided by: Amsterdam UMC, location VUmc

Tracking Information

• First Submitted Date: July 14, 2005
• First Posted Date: July 21, 2005
• Last Update Posted Date: April 25, 2006
• Study Start Date: January 2003
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (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 (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)

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MEDICLAS Study (Metabolic Effects of Different Classes of AntiretroviralS)
• Official Title: 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: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single; Primary Purpose: Prevention

Condition

• HIV Infections
• HIV-Associated Lipodystrophy Syndrome

Intervention

• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Enrollment (submitted: July 14, 2005): 50
• Original Enrollment: Same as current
• Study Completion Date: July 2008
• Primary Completion Date: Not Provided

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, Netherlands, Spain, United Kingdom

Administrative Information

• NCT Number: NCT00122226
• Other Study ID Numbers: protocol 02-72
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Amsterdam UMC, location VUmc
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: Amsterdam UMC, location VUmc
• Verification Date: July 2005