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Sponsored by: |
University of North Carolina |
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Information provided by: | The University of North Carolina, Chapel Hill |
ClinicalTrials.gov Identifier: | NCT00146068 |
The purpose of this study is to determine the safety, tolerability and efficacy of a combination therapy interferon beta-1a(Avonex) plus simvastatin (Zocor) vs. interferon beta-1a plus placebo in patients with clinically isolated syndrome suggestive of Multiple Sclerosis.
Condition | Intervention | Phase |
---|---|---|
Multiple Sclerosis |
Drug: Avonex/Zocor |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Phase IV Double-Blind Randomized Study to Evaluate Safety and Efficacy of Interferon Beta-1a (Avonex) Plus Simvastatin (Zocor) Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis Over a One Year Period |
Estimated Enrollment: | 30 |
Study Start Date: | September 2004 |
Study Completion Date: | December 2007 |
Primary Completion Date: | December 2007 (Final data collection date for primary outcome measure) |
Interferon beta-1a (IFNB-1a), a FDA approved therapy for relapsing-remitting (RR) MS has several mechanisms of action. It lowers proinflammatory cytokine production and inhibits antigen presentation by class II major histocompatibility complex (MHC) molecule. It also reduces metalloproteinase activity, which all lead to decreased migration of T-lymphocytes into the central nervous system (CNS), and subsequent inhibition of inflammatory lesion formation. We propose that combination therapy during early stages of the disease with second immunomodulatory agent that targets different steps in the pathogenesis of the disease may add to the effectiveness of IFNB-1a. IFNB-1a administered intramuscularly at 30 mg per week is particularly suitable for combination therapy due to its proven efficacy in Clinically Isolated Syndrome (CIS),favorable safety profile and low frequency of neutralizing antibodies (NABs) against IFNB-1a in comparison to other forms of IFNB-1a. Recent studies have reported a significant anti-inflammatory and neuroprotective effects of statins, cholesterol-lowering agents. Statins disrupt cellular membrane lipid rafts, which inhibit the clustering of T-cell receptor (TCR), co-stimulatory, and adhesion molecules, required for optimal T-cell activation. Along with inhibiting T-cell activation, statins decrease IFNB inducible MHC class II expression, suppressing an effective antigen presentation. They block migration of activated mononuclear cells from peripheral circulation into the CNS by blocking LFA-1 adhesion molecule and by reducing metalloproteinase type 9 secretion. While their anti-inflammatory effects at tolerable oral doses may not justify their use as monotherapy for RR MS, their pleiotropic mechanisms of action showed synergistic effects with IFNB-1a in studies in vitro. We propose that simvastatin may enhance the immunomodulatory effects of INFB-1a in patients with CIS suggestive of MS and that this combination may even more effectively prevent further disease activity if administered early in the course of the disease.
Ages Eligible for Study: | 18 Years to 60 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Subject has an abnormal screening blood test, performed at the screening visit, exceeding any of the limits defined below:
Subject has had any prior treatment with any of the following medications:
Subject has had treatment with any of the following medications within 1 year prior to randomization:
Subject has had treatment with any of the following medications:
Subject has had treatment with any of the following medications within 50 days prior to randomization:
United States, North Carolina | |
University of North Carolina-Chapel Hill MS clinic within the Neuroscience Hospital | |
Chapel Hill, North Carolina, United States, 27599 |
Principal Investigator: | Silva Markovic-Plese | The University of North Carolina, Chapel Hill |
Responsible Party: | UNC-Chapel Hill ( Silva Markovic-Plese, MD/Principal Investigator ) |
Study ID Numbers: | 04-NEUR-387 |
Study First Received: | September 1, 2005 |
Last Updated: | February 28, 2008 |
ClinicalTrials.gov Identifier: | NCT00146068 History of Changes |
Health Authority: | United States: Institutional Review Board |
Clinically Isolated Syndrome |
Antimetabolites Autoimmune Diseases Demyelinating Diseases Simvastatin Antilipemic Agents Interferons Interferon-beta |
Sclerosis Anticholesteremic Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Multiple Sclerosis Interferon beta 1a Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System |
Antimetabolites Autoimmune Diseases Disease Molecular Mechanisms of Pharmacological Action Demyelinating Diseases Immune System Diseases Simvastatin Antilipemic Agents Nervous System Diseases Enzyme Inhibitors |
Sclerosis Anticholesteremic Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Pharmacologic Actions Multiple Sclerosis Pathologic Processes Therapeutic Uses Syndrome Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System |