The MS-STAT trial: a Phase II trial of high dose simvastatin in secondary progressive multiple sclerosis

Background: Options are limited in trying to modify the disease course of secondary progressive multiple sclerosis (SPMS). An attractive candidate is the HMGCoA reductase inhibitor simvastatin, currently being evaluated in several trials in relapsing-remitting MS. The rationale for these studies is...

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Published in:Multiple sclerosis 2008-09, Vol.14, p.S36-S36
Main Authors: Chataway, J, Chan, D, Anderson, V, Polito, B, Kallis, C, Frost, C, Calder, V, Greenwood, J, Nicholas, R
Format: Article
Language:English
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Summary:Background: Options are limited in trying to modify the disease course of secondary progressive multiple sclerosis (SPMS). An attractive candidate is the HMGCoA reductase inhibitor simvastatin, currently being evaluated in several trials in relapsing-remitting MS. The rationale for these studies is the recognition that these drugs possess broad spectrum immunomodulatory and anti-inflammatory effects including inhibiting MHC class II-restricted antigen presentation, attenuating antigen-presenting cell maturation, inducing a shift from a pro-inflammatory Th1 to a regulatory Th2 phenotype, and blocking adhesion molecule expression and leukocyte migration. Germane to SPMS, recent evidence also attributes neuroprotective properties to statins such as up-regulation of the major cell survival protein bcl-2, protection against glutamate-mediated excitotoxicity and free radical damage and promotion of myelin repair. Objective: To investigate whether simvastatin can reduce the rate of brain atrophy, as measured using volumetric magnetic resonance imaging (MRI), in SPMS. Methods: A Phase II randomised placebo-controlled trial of 80mg of simvastatin in SPMS is proposed. The major inclusion criteria are: age 18-65 years, Expanded Disability Status Scale (EDSS) 4.0-6.5, progression within the previous 2 years, no immunosuppressants or disease-modifying treatments within the previous 6 months. One hundred and forty patients will be randomized (1:1) and followed up at 1 and 2 years. Brain atrophy rate will be utilized as the primary outcome measure, and will be determined from T1-weighted volumetric MRI using the brain boundary shift integral. Secondary outcome measures include changes in EDSS, MSIS-29, MSFC, SF-36, T1/T2 lesion load and cognitive function as determined by serial neuropsychological assessment. Full statin immunological profiling will be carried out. Results: This trial has now commenced. Conclusions: The results of this trial will be reported in 2011.
ISSN:1352-4585