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

Relapsing-remitting Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01111656
• Other study ID #: 75/07
• Status: Completed
• Phase: Phase 2
• First received: March 15, 2010
• Last updated: September 6, 2011
• Start date: March 2007
• Est. completion date: April 2010

Study information

• Verified date: September 2011
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: EthikkommissionSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 67 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Interferon beta-1b group
Patients receive interferon beta-1b 250ug subcutaneously every other day
• Interferon beta-1b/Atorvastatin group
Patients receive interferon beta-1b 250ug subcutaneously every other day AND atorvastatin 40mg every day (oral)

Locations

Country	Name	City	State
Switzerland	Department of Neurology, Bern University Hospital, and University of Bern	Bern

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	PharmaPart, Viollier AG, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

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. — View Citation

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with new lesions on T2-weighted images after 12 months of treatment		Month 0	Yes
Primary	Proportion of patients with new lesions on T2-weighted images after 12 months of treatment		Month 12	Yes
Secondary	Gd-enhancing lesions on T1-weighted images after 12 months of treatment.		Month 0	Yes
Secondary	Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment.		Month 0	Yes
Secondary	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	No
Secondary	Clinical disease progression (Expanded Disability Status Scale [EDSS], Multiple Sclerosis Functional Composite [MSFC] )		Month 0	Yes
Secondary	Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] )		Month 0	Yes
Secondary	Number of relapse-free patients after 12 months of treatment		Month 0	Yes
Secondary	Relapse rate after 12 months of treatment		Month 0	Yes
Secondary	Time to first relapse		Month 0	Yes
Secondary	Gd-enhancing lesions on T1-weighted images after 12 months of treatment.		Month 12	Yes
Secondary	Total T2-hyperintense lesion volume (burden of disease, BOD) after 12 months of treatment.		Month 12	Yes
Secondary	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	No
Secondary	Clinical disease progression (Expanded Disability Status Scale [EDSS] , Multiple Sclerosis Functional Composite [MSFC] )		Month 12	Yes
Secondary	Functional systems scores (of Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC] )		Month 12	Yes
Secondary	Number of relapse-free patients after 12 months of treatment		Month 12	Yes
Secondary	Relapse rate after 12 months of treatment		Month 12	Yes
Secondary	Time of first relapse		Month 12	Yes