Atorvastatin in Relapsing-Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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A phase II open-label baseline-to-treatment trial was designed to evaluate the safety, tolerability and efficacy of orally administered atorvastatin in patients with relapsing-remitting multiple sclerosis (RRMS). Patients with at least one gadolinium-enhancing lesion (CEL) at screening by magnetic resonance imaging (MRI) were eligible for the study. Patients are screened and enrolled in the outpatient clinic of the Cecilie Vogt Clinic at the Charité - University Medicine Berlin. After a baseline period of 3 monthly MRI scans (months -2 to 0), patients followed a 9-month treatment period on 80 mg atorvastatin daily. The primary endpoint is the number of CEL in treatment months 6 to 9 compared to baseline. Secondary endpoints include other MRI-based parameters and changes in clinical scores and immune responses.

Official Title
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Oral High-Dose Atorvastatin Treatment in Relapsing-Remitting Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: interferon beta treatment to add-on atorvastatin treatment
* Drug: untreated to atorvastatin treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 55 years old MS diagnosis according McDonald criteria Relapsing-remitting MS EDSS 0 - 6 Disease activity as occurrence of CEL in brain MRI IFN-beta therapy for at least 6 months Exclusion Criteria: Primary chronic progressive MS Symptoms and signs of clinical disease conditions similar to MS Conditions that can disturb MRI measurements Clinically relevant GI diseases eg Colitis ulcerosa, Crohns disease, history of Ulcus pepticum Clinically relevant lung, heart, CNS, infectious disease Clinically relevant liver, kidney or bone marrow abnormalities (as defined by specific clinical chemistry values) Allergies towards Gd-DTPA Allergies towards constituents of the therapeutic agent Recruitment to other clinical trials within 6 months prior to or during this study Pretreatment with complete lymph irradiation, antibody therapy against lymphocyte populations (eg. anti-CD4, Campath-1H), mitoxantrone, cyclophosphamide, cyclosporin A, human antibodies, all immunomodulatory or immunosuppressive agents including recombinant cytokines or other potential experimental MS therapies (6 months prior to study start), glatiramer acetate, azathioprine, IVIg (6 months prior to study start) pregnancy or lactation Alcohol or drug abuse Inhibitors of Cytochrom P 450 3A (eg. cyclosporin, macrolide antibiotics, azole antimycotics). Medical or psychological conditions that could hamper with the patients capacity to understand patient information, to give the informed consent, to adhere to the protocol of the study and to be able to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: interferon<br> | Drug: interferon beta treatment to add-on atorvastatin treatment<br>* IFN-β-1a 22 µg s.c. 3 times weekly or IFN-β-1b s.c. every other day (3 months baseline) and add on oral daily 80 mg atorvastatin (9 months add on treatment)<br>|
| Sham Comparator: untreated<br> | Drug: untreated to atorvastatin treatment<br>* no treatment(3 months baseline)and oral daily 80 mg atorvastatin (9 months add on treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of MRI contrast enhancing lesions |  | treatment months 6 to 9 compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| other MRI-based parameters (CEL volume, T2-lesion load, T1-hypointense lesion volume, whole brain magnetization transfer ratio, and apparent diffusion coefficient of normal appearing white matter) |  | treatment months 6 to 9 compared to baseline |