BMJ Open (Sep 2024)
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
- Alan J Thompson,
- Charles Wade,
- Nevin John,
- Jeremy Chataway,
- Gavin Giovannoni,
- Rachael Hunter,
- Sreedharan Harikrishnan,
- Floriana De Angelis,
- Olga Ciccarelli,
- Eli Silber,
- John Greenwood,
- Thomas Williams,
- Martin Duddy,
- Basil Sharrack,
- Annie Hawton,
- Siddharthan Chandran,
- Sue Pavitt,
- Paul Gallagher,
- Ian Galea,
- Jennifer M Nicholas,
- Tarunya Arun,
- Miriam Mattoscio,
- Richard Nicholas,
- Neil Robertson,
- Carolyn Young,
- Jeremy Hobart,
- David Rog,
- Owen Pearson,
- Anisha Doshi,
- Timothy Harrower,
- Leonora Fisniku,
- Ruth Geraldes,
- Nikos Evangelou,
- Judy Beveridge,
- Matthew Craner,
- Don Mahad,
- Stefano Pluchino,
- Suresh Chhetri,
- Susan Tebbs,
- Marie Braisher,
- Seema Kalra,
- Charles Hillier,
- Chris Frost,
- Gavin McDonnell,
- Stuart J Nixon,
- Helen L Ford,
- Jeban Ganesalingam,
- Claire Rice,
- Alberto Calvi,
- Cord Spilker,
- Abdullah Shehu,
- Martin Lee,
- James Blackstone,
- Alessia Bianchi,
- Agne Straukiene,
- Gil Barton,
- Fayyaz Ahmed,
- Dawn Lyle,
- Ekaterina Bordea,
- Sean Apap Mangion,
- Rachel Merry,
- Elisabeth Jarman
Affiliations
- Alan J Thompson
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Charles Wade
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Nevin John
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Jeremy Chataway
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Gavin Giovannoni
- Blizard Institute, Queen Mary University, London, UK
- Rachael Hunter
- Department of Primary Care and Population Health, University College London Research, London, UK
- Sreedharan Harikrishnan
- East Kent Hospitals University NHS Foundation Trust, Canterbury, UK
- Floriana De Angelis
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Olga Ciccarelli
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Eli Silber
- Department of Neurology, Lewisham and Greenwich NHS Trust, London, UK
- John Greenwood
- Institute of Ophthalmology, University College London, London, UK
- Thomas Williams
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Martin Duddy
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Basil Sharrack
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Annie Hawton
- University of Exeter, Exeter, UK
- Siddharthan Chandran
- Division of Clinical and Surgical Sciences, University of Edinburgh, Edinburgh, UK
- Sue Pavitt
- University of Leeds, Leeds, UK
- Paul Gallagher
- Queen Elizabeth University Hospital, Glasgow, UK
- Ian Galea
- Clinical & Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, UK
- Jennifer M Nicholas
- Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
- Tarunya Arun
- University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Miriam Mattoscio
- Barking Havering and Redbridge University Hospitals NHS Trust, Romford, UK
- Richard Nicholas
- Imperial College Healthcare NHS Trust, London, UK
- Neil Robertson
- University Hospital of Wales, Cardiff, UK
- Carolyn Young
- The Walton Centre NHS Foundation Trust, Liverpool, UK
- Jeremy Hobart
- University Hospitals Plymouth NHS Trust, Plymouth, UK
- David Rog
- Department of Neurology, Salford Royal NHS Foundation Trust, Salford, UK
- Owen Pearson
- Swansea Bay UHB, Swansea, UK
- Anisha Doshi
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Timothy Harrower
- Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK
- Leonora Fisniku
- University Hospitals Sussex NHS Foundation Trust, Brighton, UK
- Ruth Geraldes
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Nikos Evangelou
- Nottingham University Hospitals NHS Trust, Nottingham, UK
- Judy Beveridge
- MS Society, London, UK
- Matthew Craner
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
- Don Mahad
- Anne Rowling Regenerative Neurology Clinic, NHS Lothian, Edinburgh, UK
- Stefano Pluchino
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- Suresh Chhetri
- Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
- Susan Tebbs
- Comprehensive Clinical Trials Unit, University College London, London, UK
- Marie Braisher
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Seema Kalra
- University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
- Charles Hillier
- University Hospitals Dorset NHS Foundation Trust, Poole, UK
- Chris Frost
- Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK
- Gavin McDonnell
- Belfast City Hospital Health and Social Services Trust, Belfast, UK
- Stuart J Nixon
- MS Society, London, UK
- Helen L Ford
- Centre for Neurosciences, Leeds General Infirmary, Leeds, UK
- Jeban Ganesalingam
- University Hospitals Sussex NHS Foundation Trust, Brighton, UK
- Claire Rice
- North Bristol NHS Trust, Bristol, UK
- Alberto Calvi
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Cord Spilker
- Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
- Abdullah Shehu
- University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
- Martin Lee
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
- James Blackstone
- Comprehensive Clinical Trials Unit, University College London, London, UK
- Alessia Bianchi
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Agne Straukiene
- Torbay and South Devon NHS Foundation Trust, Torquay, UK
- Gil Barton
- Comprehensive Clinical Trials Unit, University College London, London, UK
- Fayyaz Ahmed
- Hull University Teaching Hospitals NHS Trust, Hull, UK
- Dawn Lyle
- Anne Rowling Regenerative Neurology Clinic, NHS Lothian, Edinburgh, UK
- Ekaterina Bordea
- Comprehensive Clinical Trials Unit, University College London, London, UK
- Sean Apap Mangion
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Rachel Merry
- Comprehensive Clinical Trials Unit, University College London, London, UK
- Elisabeth Jarman
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
- DOI
- https://doi.org/10.1136/bmjopen-2024-086414
- Journal volume & issue
-
Vol. 14,
no. 9
Abstract
Introduction There 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.
