effect of highdose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis msstat a randomised placebocontrolled phase 2 trial background secondary progressive multiple sclerosis for which no satisfactory treatment presently exists accounts for most of the disability in patients with multiple sclerosis simvastatin which is widely used for treatment of vascular disease with its excellent safety profile has immunomodulatory and neuroprotective properties that could make it an appealing candidate drug for patients with secondary progressive multiple sclerosismethods we undertook a doubleblind controlled trial between jan 28 2008 and nov 4 2011 at three neuroscience centres in the uk patients aged 1865 years with secondary progressive multiple sclerosis were randomly assigned 11 by a centralised webbased service with a block size of eight to receive either 80 mg of simvastatin or placebo patients treating physicians and outcome assessors were masked to treatment allocation the primary outcome was the annualised rate of wholebrain atrophy measured from serial volumetric mri analyses were by intention to treat and per protocol this trial is registered with clinicaltrialsgov number nct00647348findings 140 participants were randomly assigned to receive either simvastatin n70 or placebo n70 the mean annualised atrophy rate was significantly lower in patients in the simvastatin group 0288 per year sd 0521 than in those in the placebo group 0584 per year 0498 the adjusted difference in atrophy rate between groups was 0254 per year 95 ci 0422 to 0087 p0003 a 43 reduction in annualised rate simvastatin was well tolerated with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events 14 20 vs nine 13interpretation highdose simvastatin reduced the annualised rate of wholebrain atrophy compared with placebo and was well tolerated and safe these results support the advancement of this treatment to phase 3 testingfunding the moulton foundation charity number 1109891 berkeley foundation 268369 the multiple sclerosis trials collaboration 1113598 the rosetrees trust 298582 and a personal contribution from a pidgley uk national institute of health research nihr university college london hospitalsucl biomedical research centres funding scheme