MS-STAT2
Research type
Research Study
Full title
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
IRAS ID
232288
Contact name
Jeremy Chataway
Contact email
Sponsor organisation
University College London Comprehensive Clinical Trials Unit
Eudract number
2017-003328-56
Duration of Study in the UK
5 years, 9 months, 30 days
Research summary
Lay summary of study results: Multiple sclerosis (MS) is a lifelong condition that affects the brain and spinal cord. Many people with MS start with a type called relapsing-remitting MS, which can later become secondary progressive MS (SPMS). SPMS causes steady worsening of disability over time, and currently, there are very few treatment options for people without signs of active inflammation.
Simvastatin is a cholesterol-lowering drug (a statin) widely used for heart disease. Earlier research (the MS-STAT phase 2 trial) suggested that high-dose simvastatin might slow brain shrinkage and disability in people with SPMS. To test this further, researchers ran a large phase 3 clinical trial called MS-STAT2, involving 964 participants across the UK. Half were given simvastatin and half a placebo, and they were followed up while continuing to take these for 3 years. For participants whose disability was stable at 3 years, they could continue in the trial on the same medication for up to 4.5 years if they were happy to do so.
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The main aim was to see if simvastatin could slow down worsening disability, measured using a scale called EDSS. The EDSS data was mainly collected at face-to-face appointments, but with some assessments conducted by telephone when enforced by the COVID-19 pandemic. The results showed no significant difference between the simvastatin and placebo groups. Simvastatin did not delay disability progression. The trial also looked at other outcomes such as walking speed, hand function, memory, and quality of life. Again, there were no meaningful differences.
Importantly, simvastatin was generally safe, and side effects were rare. The trial also found that people with higher disability levels faced higher personal and financial costs, and many relied on unpaid care from family or friends.Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the UK and 2.5 million people globally. Most people with MS experience two stages of the disease: \nEarly MS – Relapsing-Remitting MS (RRMS), which is partially reversible, and \nLate MS – Secondary Progressive MS (SPMS), which affects the majority of patients, usually after 10 to 15 years after diagnosis. \nSPMS results from progressive neuronal degeneration that causes accumulating and irreversible disability affecting walking, balance, manual function, vision, cognition, pain control, bladder and bowel function. The pathological process driving the accrual of disability in SPMS is not known at present.\n\nImmunomodulatory anti-inflammatory disease modifying therapies (DMTs) are increasingly effective in reducing relapse frequency in RRMS, however, they have been unsuccessful in slowing disease progression in SPMS. This is the overwhelming conclusion from an analysis of 18 phase 3 trials (n=8500), of which 70% of the population had SPMS, all performed in the last 25 years. There is no current disease modifying treatment (DMT) for SPMS.\nIn an earlier study (MS-STAT1), 140 people with SPMS were randomly assigned to receive either placebo or simvastatin for a period of two years. The investigators found that the rate of brain atrophy (loss of neurons - ‘brain shrinkage’), as measured by magnetic resonance imaging (MRI), was reduced in patients receiving simvastatin compared to those taking placebo.\nSeveral other long term studies have also reported that there might be a relationship between the rate of brain atrophy and the degree of impairment. \n\nThe study is designed to test the effectiveness of repurposed simvastatin (80mg) in a phase 3 double blind, randomised, placebo controlled trial (1:1) in patients with secondary progressive MS (SPMS), to determine if the rate of disability progression can be slowed over a 3 year period. COVID 19 amendment 27/04/2020 The MHRA feedback received via helpline (17-Mar-2020) was that in light of the ongoing public health situation (Covid-19 outbreak), flexibility on the existing 6-monthly window was strongly supported, particularly with respect to this vulnerable population group (patients with Secondary Progressive MS), for whom current guidance from PHE is that they should limit unnecessary contact where possible.
REC name
London - Westminster Research Ethics Committee
REC reference
17/LO/1509
Date of REC Opinion
9 Oct 2017
REC opinion
Favourable Opinion