Effect of high-dose simvastatin on cognition in secondary progressive multiple sclerosis (MS-STAT cognitive): a randomised, placebo-controlled, Phase 2 trial
Author(s): ,
D Chan
Affiliations:
Brighton and Sussex Medical School, Brighton;Cambridge University, Cambridge
,
S Binks
Affiliations:
Brighton and Sussex Medical School, Brighton
,
J Nicholas
Affiliations:
London School of Hygiene and Tropical Medicine
,
C Frost
Affiliations:
London School of Hygiene and Tropical Medicine
,
A Alsanousi
Affiliations:
Imperial College London
,
N Fox
Affiliations:
University College London
,
D Wilkie
Affiliations:
Imperial College London
,
R Nicholas
Affiliations:
Imperial College London
,
J Chataway
Affiliations:
Queen Square Multiple Sclerosis Centre, University College London, London, United Kingdom
MS-STAT Trialists
MS-STAT Trialists
Affiliations:
ECTRIMS Online Library. Chataway J. Sep 16, 2016; 147068; 226
Jeremy Chataway
Jeremy Chataway
Contributions
Abstract

Abstract: 226

Type: Oral

Abstract Category: Pathology and pathogenesis of MS - Neuropsychology

Background: Cognitive impairment is a major contributor to disability and reduced quality of life in secondary progressive MS (SPMS). In the 24 month MS-STAT phase 2 trial we showed that high dose simvastatin significantly reduced the rate of whole brain atrophy, as well as demonstrating effects on clinician and patient observed outcome measures. We describe here results of the MS-STAT cognitive sub-study.

Objectives: 140 patients with SPMS, with Expanded Disability Severity Scale (EDSS) scores between 4-6.5, were randomised to receive simvastatin (n=70) or placebo (n=70). Full cognitive and neuropsychiatric testing was undertaken at study entry,12 and 24 months.

Methods: The following cognitive domains were tested: premorbid IQ; general intellectual functioning; verbal and nonverbal memory; semantic memory; visual perceptual function; attention, speed of information processing, and working memory (PASAT-3); frontal lobe function (frontal assessement battery, FAB). Neuropsychiatric symptoms were assessed using the Hamilton Depression Scale and the Neuropsychiatric Inventory Questionnaire. Linear mixed models were used to examine how the scores changed between baseline, 12 and 24 months and the difference in score between the placebo and simvastatin group at 12 and 24 months.

Results: Baseline assessment revealed nearly half of patients had frontal lobe impairment. There were also significant numbers of patients (up to 33%) with impairment on tests of verbal and nonverbal memory. Over the entire trial, the whole cohort declined on tests of verbal and non-verbal memory. At 24 months, there was a significant difference in FAB scores between the two treatment groups, with a 0.24 point increase in the mean FAB score observed in the active arm, compared with a decline of 0.92 points in the placebo group: a difference of 1.08 ( 95% CI 0.09 to 2.14). No treatment effect was observed on any other cognitive or neuropsychiatric measure.

Conclusion: This represents the largest SPMS published cohort to have been studied with longitudinal cognitive and neuropsychiatric assessments. Frequent cognitive impairment was observed at study entry, with decline at 24 months observed primarily in episodic memory. Although the results must be interpreted carefully because of the many variables examined, we found that high dose simvastatin significantly improves frontal lobe function, adding to our previous observation of a positive treatment effect on brain atrophy rates.

Disclosure:

D Chan:funded by the Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre and receives grant income from Alzheimer"s Research UK, the Isaac Newton Trust, Innovate UK and the UK Medical Research Council.

S Binks:holds a NIHR academic clinical fellowship.

J Nicholas:funded by the Multiple Sclerosis Trials Collaboration (MSTC) for this work. C Frost:nothing to disclose.

A Alsanousi:funded by the MSTC for this work.

N Fox:support from an Medical Research Council Senior Fellowship, an NIHR Senior Investigator award, the NIHR Queen Square Biomedical Research Unit in Dementia and the Wolfson Foundation.

D Wilkie:nothing to disclose.

R Nicholas:funded by MSTC for this work. Bayer, Biogen, Genzyme, Merck Serono, Roche - honorarium for speaking, advisory boards. Biogen, Genzyme, Novartis - funds for organising education, staff. Biogen, Novartis - Principal investigator.

J Chatway:NIHR University College London Hospitals/UCL Biomedical Research Centres funding scheme. The Moulton Foundation, Berkeley Foundation, MSTC. Local principal investigator for trials in multiple sclerosis funded by Novartis, Biogen, and GSK. Investigator grant from Novartis outside this work. Advisory Boards for Roche and Merck.

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