Evidence map›Paper›PMID 39284697›Full record

ArticleBMJ open2024

Evaluating the effectiveness of simvastatin in slowing the progression of disability in secondary progressive multiple sclerosis (MS-STAT2): protocol for a multicentre, randomised controlled, double-blind, phase 3 clinical trial in the UK.

James Blackstone, Thomas Williams, Jennifer M Nicholas, Ekaterina Bordea, Floriana De Angelis, Alessia Bianchi, Alberto Calvi, Anisha Doshi, Nevin John, Sean Apap Mangion and 52 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03387670 (A Phase 3 Randomised, Double Blind, Clinical Trial Investigating the Effectiveness of Repurposed Simvastatin Compared to Placebo, in Secondary Progressive Multiple Sclerosis, in Slowing the Progression of Disability), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03387670 phase3completednot on this map

A Phase 3 Randomised, Double Blind, Clinical Trial Investigating the Effectiveness of Repurposed Simvastatin Compared to Placebo, in Secondary Progressive Multiple Sclerosis, in Slowing the Progression of Disability

TypeinterventionalSponsorUniversity College, LondonRan2018 to 2024Enrolled964ConditionsSecondary Progressive Multiple Sclerosis (SPMS)ArmsSimvastatin, Placebo
3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  9. Repair mechanisms of the central nervous system: From axon sprouting to remyelination.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  10. Review
  11. Review
  12. Treating comorbidities in MS is disease modifying: Commentary.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. Towards Treating Multiple Sclerosis Progression.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

62 authors.

James BlackstoneComprehensive Clinical Trials Unit, University College London, London, UK.ORCID 0000-0003-4335-5269
Thomas WilliamsQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Jennifer M NicholasMedical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Ekaterina BordeaComprehensive Clinical Trials Unit, University College London, London, UK.
Floriana De AngelisQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Alessia BianchiQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Alberto CalviQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Anisha DoshiQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Nevin JohnQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Sean Apap MangionQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Charles WadeQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Rachel MerryComprehensive Clinical Trials Unit, University College London, London, UK.
Gil BartonComprehensive Clinical Trials Unit, University College London, London, UK.
Dawn LyleAnne Rowling Regenerative Neurology Clinic, NHS Lothian, Edinburgh, UK.
Elisabeth JarmanUniversity Hospital Southampton NHS Foundation Trust, Southampton, UK.
Don MahadAnne Rowling Regenerative Neurology Clinic, NHS Lothian, Edinburgh, UK.
Abdullah ShehuUniversity Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
Tarunya ArunUniversity Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.
Gavin McDonnellBelfast City Hospital Health and Social Services Trust, Belfast, UK.
Ruth GeraldesOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Matthew CranerOxford University Hospitals NHS Foundation Trust, Oxford, UK.
Charles HillierUniversity Hospitals Dorset NHS Foundation Trust, Poole, UK.
Jeban GanesalingamUniversity Hospitals Sussex NHS Foundation Trust, Brighton, UK.
Leonora FisnikuUniversity Hospitals Sussex NHS Foundation Trust, Brighton, UK.
Jeremy HobartUniversity Hospitals Plymouth NHS Trust, Plymouth, UK.
Cord SpilkerBradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Neil RobertsonUniversity Hospital of Wales, Cardiff, UK.
Seema KalraUniversity Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK.
Stefano PluchinoCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Sreedharan HarikrishnanEast Kent Hospitals University NHS Foundation Trust, Canterbury, UK.
Miriam MattoscioBarking Havering and Redbridge University Hospitals NHS Trust, Romford, UK.
Timothy HarrowerRoyal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Carolyn YoungThe Walton Centre NHS Foundation Trust, Liverpool, UK.
Martin LeeNorfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
Suresh ChhetriLancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.
Fayyaz AhmedHull University Teaching Hospitals NHS Trust, Hull, UK.
David RogDepartment of Neurology, Salford Royal NHS Foundation Trust, Salford, UK.
Eli SilberDepartment of Neurology, Lewisham and Greenwich NHS Trust, London, UK.
Paul GallagherQueen Elizabeth University Hospital, Glasgow, UK.
Martin DuddyNewcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Agne StraukieneTorbay and South Devon NHS Foundation Trust, Torquay, UK.
Richard NicholasImperial College Healthcare NHS Trust, London, UK.
Claire RiceNorth Bristol NHS Trust, Bristol, UK.
Stuart J NixonMS Society, London, UK.
Judy BeveridgeMS Society, London, UK.
Annie HawtonUniversity of Exeter, Exeter, UK.
Susan TebbsComprehensive Clinical Trials Unit, University College London, London, UK.
Marie BraisherQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Gavin GiovannoniBlizard Institute, Queen Mary University, London, UK.ORCID 0000-0001-9995-1700
Olga CiccarelliQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
John GreenwoodInstitute of Ophthalmology, University College London, London, UK.
Alan J ThompsonQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Rachael HunterDepartment of Primary Care and Population Health, University College London Research, London, UK.ORCID 0000-0002-7447-8934
Sue PavittUniversity of Leeds, Leeds, UK.
Owen PearsonSwansea Bay UHB, Swansea, UK.
Nikos EvangelouNottingham University Hospitals NHS Trust, Nottingham, UK.
Basil SharrackSheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
Ian GaleaClinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK.ORCID 0000-0002-1268-5102
Siddharthan ChandranAnne Rowling Regenerative Neurology Clinic, NHS Lothian, Edinburgh, UK.ORCID 0000-0001-6827-1593
Helen L FordCentre for Neurosciences, Leeds General Infirmary, Leeds, UK.ORCID 0000-0002-4156-5046
Chris FrostMedical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Jeremy ChatawayQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK j.chataway@ucl.ac.uk.ORCID 0000-0001-7286-6901

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThere remains a high unmet need for disease-modifying therapies that can impact disability progression in secondary progressive multiple sclerosis (SPMS). Following positive results of the phase 2 MS-STAT study, the MS-STAT2 phase 3 trial will evaluate the efficacy and cost-effectiveness of repurposed high-dose simvastatin in slowing the progression of disability in SPMS. METHODS AND ANALYSIS: MS-STAT2 will be a multicentre, randomised, placebo-controlled, double-blind trial of participants aged between 25 and 65 (inclusive) who have SPMS with an Expanded Disability Status Scale (EDSS) score of 4.0-6.5 (inclusive). Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years.Participants will be allocated to simvastatin or placebo in a 1:1 ratio. The active treatment will be 80 mg daily, after 1 month at 40 mg daily. 31 hospitals across the UK will participate.The primary outcome is (confirmed) disability progression at 6 monthly intervals, measured as change from EDSS baseline score. Recruitment of 1050 participants will be required to achieve a total of 330 progression events, giving 90% power to demonstrate a 30% relative reduction in disability progression versus placebo. The follow-up period is 36 months, extendable by up to 18 months for patients without confirmed progression.Clinician-reported measures include Timed 25 Foot Walk; 9 Hole Peg Test; Single Digit Modalities Test; Sloan Low Contrast Visual Acuity; Relapse assessment; modified Rankin Scale and Brief International Cognitive Assessment For Multiple Sclerosis. Patient-reported outcomes include MS-specific walking, fatigue and impact scales. A health economic analysis will occur. ETHICS AND DISSEMINATION: The protocol was approved by the London-Westminster REC (17/LO/1509). This manuscript is based on protocol version 8.0, 26 February 2024. Trial findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBERS: NCT03387670; ISRCTN82598726.

Indexed as

Disease ProgressionMultiple Sclerosis, Chronic ProgressiveSimvastatinAdultAgedClinical Trials, Phase III as TopicCost-Benefit AnalysisDisability EvaluationDouble-Blind MethodFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiddle AgedMulticenter Studies as TopicRandomized Controlled Trials as TopicHydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinClinical TrialDrug TherapyMultiple sclerosis

Identifiers

PMID39284697
PMCPMC11409264

What Socratic holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.