Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

被引:89
|
作者
Chan, Dennis [1 ,2 ]
Binks, Sophie [3 ]
Nicholas, Jennifer M. [4 ]
Frost, Chris [4 ]
Cardoso, M. Jorge [5 ]
Ourselin, Sebastien [5 ]
Wilkie, David [7 ]
Nicholas, Richard [7 ]
Chataway, Jeremy [6 ]
机构
[1] Brighton & Sussex Med Sch, Brighton, E Sussex, England
[2] Univ Cambridge, Dept Clin Neurosci, Cambridge, England
[3] Brighton & Sussex Univ Hosp NHS Trust, Brighton, E Sussex, England
[4] London Sch Hyg & Trop Med, London, England
[5] UCL, Ctr Med Image Comp, London, England
[6] UCL, Queen Sq Multiple Sclerosis Ctr, Dept Neuroinflammat, Inst Neurol, London WC1B 5EH, England
[7] Imperial Coll London, London, England
来源
LANCET NEUROLOGY | 2017年 / 16卷 / 08期
关键词
IMPAIRMENT; DISABILITY; DYSFUNCTION; ATROPHY; BURDEN;
D O I
10.1016/S1474-4422(17)30113-8
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. Methods We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1: 1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the selfreported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Findings Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5.7 points, 95% CI 3.6-7.8; p<0.0001) and non-verbal memory (decline of 6.8 points, 4.8-8.7; p<0.0001). At 24 months, the FAB score was 12 points higher in the simvastatin-treated group than in the placebo group (95% CI 0.2-2.3). The simvastatin group also had a 2.5 points better mean physical component score of the SF-36 (95% CI 0.3-48; p=0.028). A treatment effect was not noted for any other outcomes. Interpretation To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials. Funding The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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收藏
页码:591 / 600
页数:10
相关论文
共 42 条
  • [1] Effect of high-dose simvastatin on cognition in secondary progressive multiple sclerosis (MS-STAT cognitive): a randomised, placebo-controlled, Phase 2 trial.
    Chan, D.
    Binks, S.
    Nicholas, J.
    Frost, C.
    Alsanousi, A.
    Fox, N.
    Wilkie, D.
    Nicholas, R.
    Chataway, J.
    [J]. MULTIPLE SCLEROSIS JOURNAL, 2016, 22 : 82 - 83
  • [2] Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial
    Chataway, Jeremy
    Schuerer, Nadine
    Alsanousi, Ali
    Chan, Dennis
    MacManus, David
    Hunter, Kelvin
    Anderson, Val
    Bangham, Charles R. M.
    Clegg, Shona
    Nielsen, Casper
    Fox, Nick C.
    Wilkie, David
    Nicholas, Jennifer M.
    Calder, Virginia L.
    Greenwood, John
    Frost, Chris
    Nicholas, Richard
    [J]. LANCET, 2014, 383 (9936): : 2213 - 2221
  • [3] The MS-STAT trial: a randomised placebo-controlled phase II trial of high dose simvastatin in secondary progressive multiple sclerosis (SPMS)
    Chataway, J.
    Alsanousi, A.
    Chan, D.
    Macmanus, D.
    Hunter, K.
    Foster, J.
    Bangham, C.
    Wilkie, D.
    Nicholas, J.
    Calder, V.
    Greenwood, J.
    Frost, C.
    Nicholas, R.
    [J]. EUROPEAN JOURNAL OF NEUROLOGY, 2012, 19 : 87 - 87
  • [4] The MS-STAT trial: a Phase II trial of high dose simvastatin in secondary progressive multiple sclerosis
    Chataway, Jeremy
    Chan, Dennis
    Anderson, Val
    Polito, Bella
    Kallis, Constantinos
    Frost, Chris
    Calder, Virginia
    Greenwood, John
    Nicholas, Richard
    [J]. MULTIPLE SCLEROSIS, 2008, 14 : S36 - S37
  • [5] THE MS-STAT TRIAL: A PHASE II TRIAL OF HIGH-DOSE SIMVASTATIN FOR SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS: BASELINE TRIAL PROFILE
    Chataway, J.
    Anderson, V.
    Chan, D.
    Frost, C.
    Hunter, K.
    Kallis, C.
    Greenwood, J.
    Schuerer, N.
    Alsanousi, A.
    Nicholas, R.
    [J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2010, 81 (11): : E55 - E55
  • [6] THE MS-STAT TRIAL: High Dose Simvastatin Slows Brain Atrophy and Delays Disability in Secondary Progressive Multiple Sclerosis: A Phase II Placebo-Controlled Trial
    Chataway, Jeremy
    Schuerer, Nadine
    Alsanousi, Ali
    Chan, Dennis
    MacManus, David
    Hunter, Kelvin
    Anderson, Val
    Foster, Jo
    Bangham, Charles
    Clegg, Shona
    Nielsen, Casper
    Fox, Nick
    Wilkie, David
    Nicholas, Jennifer
    Calder, Virginia
    Greenwood, John
    Frost, Chris
    Nicholas, Richard
    [J]. NEUROLOGY, 2013, 80
  • [7] The MS-STAT Trial: A Phase II Trial of High Dose Simvastatin for Secondary Progressive Multiple Sclerosis (SPMS): Initial Results
    Chataway, Jeremy S.
    Alsanousi, Ali
    Chan, Dennis
    MacManus, David
    Hunter, Kelvin
    Foster, Jo
    Bangham, Charles
    Wilkie, David
    Nicholas, Jennifer
    Calder, Virginia
    Greenwood, John
    Frost, Chris
    Nicholas, Richard
    [J]. ANNALS OF NEUROLOGY, 2012, 72 : S111 - S111
  • [8] Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial
    Williams, Thomas
    Tur, Carmen
    Eshaghi, Arman
    Doshi, Anisha
    Chan, Dennis
    Binks, Sophie
    Wellington, Henny
    Heslegrave, Amanda
    Zetterberg, Henrik
    Chataway, Jeremy
    [J]. MULTIPLE SCLEROSIS JOURNAL, 2022, 28 (12) : 1913 - 1926
  • [9] The MS-STAT trial: high dose simvastatin demonstrates neuroprotection without immune-modulation in secondary progressive multiple sclerosis (SPMS) - a phase II trial
    Chataway, J.
    Alsanousi, A.
    Chan, D.
    MacManus, D.
    Hunter, K.
    Foster, J.
    Bangham, C.
    Wilkie, D.
    Nicholas, J.
    Clegg, S.
    Nielsen, C.
    Scheurer, N.
    Calder, V.
    Greenwood, J.
    Frost, C.
    Nicholas, R.
    [J]. MULTIPLE SCLEROSIS JOURNAL, 2012, 18 : 509 - 509
  • [10] MS-STAT2: A PHASE 3 TRIAL OF HIGH DOSE SIMVASTATIN IN SECONDARY PROGRESSIVE MULTIPLE SCLEROSIS
    Williams, E.
    John, N. A.
    Blackstone, J.
    Brownlee, W.
    Frost, C.
    Greenwood, J.
    Chataway, J.
    [J]. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2019, 90 (03): : E13 - E13