Efficacy, Safety and Tolerability of Atorvastatin 40 mg in Patients With Relapsing-remitting Multiple Sclerosis Treated With Interferon-beta-1b

Study Description

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Brief Summary:

The "SWiss Atorvastatin and Interferon-Beta 1b Trial In Multiple Sclerosis - Follow up Study" is the follow up study of the "SWiss Atorvastatin and Interferon Beta-1b Trial In Multiple Sclerosis (SWABIMS)" (see http://www.clinicaltrials.gov. Identifier: NCT00942591) SWABIMS evaluated the efficacy, safety and tolerability of atorvastatin 40 mg in addition to interferon-beta 1b compared to interferon-beta 1b monotherapy in patients with relapsing-remitting multiple sclerosis for 15 month. The SWABIMS Follow up study observes patients that finish the SWABIMS study for another 12 month with ongoing unchanged medication.

Condition or disease	Intervention/treatment	Phase
Relapsing-remitting Multiple Sclerosis	Drug: Interferon beta-1b group; Drug: Interferon beta-1b/Atorvastatin group	Phase 2

Detailed Description:

Background

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system. Statins are lipid-lowering drugs which inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA-) reductase, which is the main regulatory enzyme of cholesterol biosynthesis. In recent years many studies have demonstrated, that statins have anti-inflammatory and immunomodulatory properties in addition to their lipid-lowering effects. Therefore, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Studies in experimental allergic encephalomyelitis (EAE), the animal model for the human demyelinating disease multiple sclerosis, as well as smaller studies in patients with relapsing-remitting multiple sclerosis showed beneficial effect on the course of the disease. But there are also reports of negative impact of statins on multiple sclerosis. Therefore, bigger studies are needed to investigate the therapeutical potential of statins in multiple sclerosis.

Objective

To assess the efficacy, safety and tolerability of the combination of atorvastatin 40mg p.o. daily and interferon-beta 1b sc e.o.d compared to monotherapy with interferon-beta-1b sc e.o.d in patients with relapsing-remitting multiple sclerosis for 12 month after completing the SWABIMS study.

Methods

Multi-center, rater-blinded, parallel-group, two arm, randomized study. Patients with relapsing-remitting forms of MS, respecting all inclusion/exclusion criteria, were randomized in the SWABIMS study in two equal-size parallel arms after three months of treatment with interferon-beta 1b, receiving atorvastatin 40mg/d or not in addition to interferon-beta 1b for 12 month.

After successful completion of the study, patients were asked to participate in the "SWABIMS Follow up study" for another 12 month with ongoing medication.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	28 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	SWiss Atorvastatin and Interferon-Beta 1b Trial In Multiple Sclerosis - Follow up Study ("SWABIMS Follow Up-study")
Study Start Date :	March 2007
Actual Primary Completion Date :	April 2010
Actual Study Completion Date :	April 2010

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 1; Interferon beta-1b 250ug subcutaneously every other day	Drug: Interferon beta-1b group; Patients receive interferon beta-1b 250ug subcutaneously every other day
Experimental: 2; Interferon beta-1b 250ug subcutaneously every other day AND atorvastatin 40mg every day (oral)	Drug: Interferon beta-1b/Atorvastatin group; Patients receive interferon beta-1b 250ug subcutaneously every other day AND atorvastatin 40mg every day (oral)

Outcome Measures

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Primary Outcome Measures :

1. Proportion of patients with new lesions on T2-weighted images after 12 months of treatment [ Time Frame: Month 0 ]
2. Proportion of patients with new lesions on T2-weighted images after 12 months of treatment [ Time Frame: Month 12 ]

Secondary Outcome Measures :

1. Gd-enhancing lesions on T1-weighted images after 12 months of treatment. [ Time Frame: Month 0 ]
2. Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. [ Time Frame: Month 0 ]
3. Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI) after 12 months of treatment [ Time Frame: Month 0 ]
4. Clinical disease progression (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 0 ]
5. Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 0 ]
6. Number of relapse-free patients after 12 months of treatment [ Time Frame: Month 0 ]
7. Relapse rate after 12 months of treatment [ Time Frame: Month 0 ]
8. Time to first relapse [ Time Frame: Month 0 ]
9. Gd-enhancing lesions on T1-weighted images after 12 months of treatment. [ Time Frame: Month 12 ]
10. Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. [ Time Frame: Month 12 ]
11. Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI)after 12 months of treatment [ Time Frame: Month 12 ]
12. Clinical disease progression (Expanded Disability Status Scale [EDSS] , Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 12 ]
13. Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) [ Time Frame: Month 12 ]
14. Number of relapse-free patients after 12 months of treatment [ Time Frame: Month 12 ]
15. Relapse rate after 12 months of treatment [ Time Frame: Month 12 ]
16. Time of first relapse [ Time Frame: Month 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 67 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Successful completion of the SWABIMS study
• Written informed consent

Exclusion Criteria

• Any disease other than multiple sclerosis that would better explain the patient's signs and symptoms
• Secondary progressive MS
• Uncontrolled severe medical disorder
• Participation in any other studies

Contacts and Locations

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Locations

Switzerland
Department of Neurology, Bern University Hospital, and University of Bern
Bern, Switzerland, 3007

Sponsors and Collaborators

University Hospital Inselspital, Berne

Viollier AG, Basel, Switzerland

PharmaPart

Investigators

Principal Investigator:	Heinrich Mattle, Prof.	Dep. of Neurology, Bern University Hospital

More Information

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Publications:

Kamm CP, Mattle HP; SWABIMS Study Group. SWiss Atorvastatin and interferon Beta-1b trial In Multiple Sclerosis (SWABIMS)--rationale, design and methodology. Trials. 2009 Dec 14;10:115. doi: 10.1186/1745-6215-10-115.

Youssef S, Stüve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002 Nov 7;420(6911):78-84.

Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000 Dec;6(12):1399-402.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kamm CP, El-Koussy M, Humpert S, Findling O, Burren Y, Schwegler G, Donati F, Müller M, Müller F, Slotboom J, Kappos L, Naegelin Y, Mattle HP; SWABIMS Study Group. Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial. PLoS One. 2014 Jan 30;9(1):e86663. doi: 10.1371/journal.pone.0086663. eCollection 2014.

Responsible Party:	Prof. H. Mattle, Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland
ClinicalTrials.gov Identifier:	NCT01111656 History of Changes
Other Study ID Numbers:	75/07
First Posted:	April 27, 2010
Last Update Posted:	September 7, 2011
Last Verified:	September 2011

Keywords provided by University Hospital Inselspital, Berne:

Multi-center; randomized; prospective	parallel-group; rater-blinded; RR-MS

Additional relevant MeSH terms:

Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Interferons; Interferon-beta; Atorvastatin Calcium; Interferon beta-1b	Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic