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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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SWiss Atorvastatin and Interferon-Beta 1b Trial In Multiple Sclerosis - Follow up Study (SWABIMS Follow Up-study)

Conditions
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Relapsing-remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Interferon beta-1b group
* Drug: Interferon beta-1b/Atorvastatin group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Interferon beta-1b 250ug subcutaneously every other day | Drug: Interferon beta-1b group<br>* Patients receive interferon beta-1b 250ug subcutaneously every other day<br>|
| Experimental: 2<br>Interferon beta-1b 250ug subcutaneously every other day AND atorvastatin 40mg every day (oral) | Drug: Interferon beta-1b/Atorvastatin group<br>* Patients receive interferon beta-1b 250ug subcutaneously every other day AND atorvastatin 40mg every day (oral)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with new lesions on T2-weighted images after 12 months of treatment |  | Month 0 | 
| Proportion of patients with new lesions on T2-weighted images after 12 months of treatment |  | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gd-enhancing lesions on T1-weighted images after 12 months of treatment. |  | Month 0 | 
| Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. |  | Month 0 | 
| Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI) after 12 months of treatment |  | Month 0 | 
| Clinical disease progression (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC] ) |  | Month 0 | 
| Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) |  | Month 0 | 
| Number of relapse-free patients after 12 months of treatment |  | Month 0 | 
| Relapse rate after 12 months of treatment |  | Month 0 | 
| Time to first relapse |  | Month 0 | 
| Gd-enhancing lesions on T1-weighted images after 12 months of treatment. |  | Month 12 | 
| Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment. |  | Month 12 | 
| Cortical atrophy (changes in brain volume, changes in grey matter and white matter) on magnetic resonance imaging (MRI)after 12 months of treatment |  | Month 12 | 
| Clinical disease progression (Expanded Disability Status Scale [EDSS] , Multiple Sclerosis Functional Composite [MSFC] ) |  | Month 12 | 
| Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] ) |  | Month 12 | 
| Number of relapse-free patients after 12 months of treatment |  | Month 12 | 
| Relapse rate after 12 months of treatment |  | Month 12 | 
| Time of first relapse |  | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multi-center, randomized, prospective, parallel-group, rater-blinded, RR-MS