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Secondary Progressive Multiple Sclerosis (SPMS)Phase 3MS-STAT2NCT03387670

Multiple Sclerosis-Simvastatin Trial 2

A Phase 3 study testing Simvastatin in people with Secondary Progressive Multiple Sclerosis (SPMS), run by University College, London at 31 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the United Kingdom and 2.5 million people globally. Read more about this study

Who is it for?
Ages 25 to 65 years
What is being tested?
Simvastatin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
964 participants
Where
31 sitesUnited Kingdom
Study dates
28 Mar 2018to 25 Aug 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with a confirmed diagnosis of multiple sclerosis (MS) that have entered the secondary progressive stage. Steady progression rather than relapse must be the major cause of increasing disability in the preceding 2 years. Progression can be evident from either an increase of at least 1 point if EDSS score \<6, or an increase of 0.5 point if EDSS score ≥6, or clinical documentation of increasing disability;
  • EDSS 4.0 - 6.5 (inclusive);
  • Aged 25 to 65 years old;
  • Patients must be able and willing to comply with the terms of this protocol;
  • Written informed consent provided.

Who cannot join

  • Relapse within 3 months of baseline visit. Patients will be eligible where 3 months from the final day of the relapse, has elapsed by the date of the baseline visit;
  • Patients that have been treated with steroids (intravenous and/or oral) due to MS relapse/progression within 3 months from the final day of relapse to the baseline visit. These patients may undergo a further screening visit once the 3 month window has expired and may be included if no steroid treatment has been administered in the intervening period; (Note: Patients on steroids for another medical condition may be included in the trial provided the steroid prescription is not for MS relapse/progression)
  • Significant organ co-morbidity e.g. cardiac failure, renal failure, malignancy;
  • Screening levels of alanine aminotransferase (ALT) / aspartate aminotransferase (AST) or creatine kinase (CK) ≥3 x upper limit of normal (ULN);
  • Current use of a statin; or any use within the last 6 months;
  • Medications that interact unfavourably with simvastatin as outlined in the current summary of product characteristics (SmPC); including but not limited to CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, fluconazole, HIV protease inhibitors (e.g. nelfinavir), boceprevir, erythromycin, clrithromycin, telithromycin, telaprevir, nefazodone, fibrates (including fenofibrates), nicotinic acid (or products containing niacin), azole anti-fungal preparations, macrolide antibiotics, protease inhibitors, verapamil, amiodarone, amlodipine, gemfibrozil, ciclosporin, danazol, diltiazem, rifampicin, fusidic acid, elbasvir, grazoprevir,ticagrelor, daptomycin, grapefruit juice or alcohol abuse;
Show all 17Show fewer
  • Primary progressive MS;
  • Diabetes mellitus type 1;
  • Uncontrolled hypothyroidism;
  • Female participants that are pregnant or breast feeding. Women of child bearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, and up to 4 weeks after the last dose of study drug;
  • Use of immunosuppressants (e.g. azathioprine, methotrexate, ciclosporine) or disease modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months;
  • Use of mitoxantrone, natalizumab, alemtuzumab, daclizumab or other monoclonal antibody treatment, if treated within the last 12 months;
  • Use of fingolimod, dimethyl fumarate, teriflunomide, cladribine within the last 12 months;
  • Use of other experimental disease modifying treatment within the last 6 months;
  • Commencement of fampridine ≤6 months from day of randomisation;
  • Concurrent participation in another clinical trial of an investigational medicinal product or medical device;
  • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Trial locations and contacts

31 sites in 1 country.

31 sites in 1 country

United Kingdom31 sites

  • Belfast City Hospital

    Belfast, BT9 7AB

  • St Luke s Hospital

    Bradford, BD5 ONA

  • Royal Sussex County Hospital

    Brighton, BN2 5BE

  • Southmead Hospital

    Bristol, BS10 5NB

  • Addenbrooke's Hospital

    Cambridge, CB2 0QQ

  • Kent and Canterbury Hospital

    Canterbury, CT1 3NG

  • University Hospital of Wales

    Cardiff, CF14 4XW

  • University Hospital Coventry and Warwickshire

    Coventry, CV2 2DX

  • The Anne Rowling Regenerative Neurology Clinic

    Edinburgh, EH16 4SB

  • Royal Devon and Exeter Hospital

    Exeter, EX2 5DW

  • The Queen Elizabeth University Hospital

    Glasgow, G51 4TF

  • Hull Royal Infirmary

    Hull, HU3 2JZ

  • Leeds General Infirmary

    Leeds, LS1 3EX

  • The Walton Centre NHS Foundation Trust

    Liverpool, L9 7LJ

  • Queen's Hospital, Barking, Havering and Redbridge University Hospitals

    London, RM7 0AG

  • Queen Elizabeth Hospital

    London, SE18 4QH

  • Charing Cross Hospital

    London, W6 8RF

  • University College London Hospital

    London, WC1N 3BG

  • Salford Royal Hospital

    Manchester, M6 8HD

  • Royal Victoria Infirmary

    Newcastle upon Tyne, NE1 4LP

  • Norfolk and Norwich University Hospital

    Norwich, NR4 7UY

  • Queen's Medical Centre

    Nottingham, NG7 2UH

  • John Radcliffe Hospital

    Oxford, OX3 9DU

  • Derriford Hospital

    Plymouth, PL6 8BH

  • Poole Hospital

    Poole, BH15 2JB

  • Royal Preston Hospital

    Preston, PR2 9HT

  • Royal Hallamshire Hospital

    Sheffield, S10 2JF

  • Southampton General Hospital

    Southampton, SO16 6YD

  • University Hospital of North Staffordshire

    Stoke-on-Trent, ST4 6QG

  • Morriston & Neath Port Talbot Hospitals (Abertawe Bro Morgannwg University Local Health Board)

    Swansea

  • Torbay Hospital

    Torquay, TQ2 7AA

Other trials in United Kingdom

About this study

Official 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

Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the United Kingdom and 2.5 million people globally. Most people with MS experience two stages of the disease:

Early MS - Relapsing-Remitting MS (RRMS), which is partially reversible, and Late MS - Secondary Progressive MS (SPMS), which affects the majority of patients, usually after 10 to 15 years after diagnosis.

Read more

SPMS 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.

Immunomodulatory 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.

In an earlier study (Multiple Sclerosis-Simvastatin 1; 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.

Several other long term studies have also reported that there might be a relationship between the rate of brain atrophy and the degree of impairment. The 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 to 4.5 year period.

The results generated from this trial may help to improve the treatment options of people with MS. In addition, taking part in this trial will mean regular review by an experienced neurologist regardless of the drug that patients are randomly allocated to receive.

Being tested
Simvastatin, Placebo
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SimvastatinDrug

    • One (1 = 40mg) simvastatin tablet once daily at night for 1 month
    • Two (2 = 80mg) simvastatin tablets once daily at night, for the next 35 to 53 months

  • PlaceboDrug

    • One (1) placebo tablet once daily at night for 1 month
    • Two (2) placebo tablets once daily at night, for the next 35 to 53 months
Study groups in NCT03387670
Study groupRoleWhat they receive
SimvastatinActive comparatorNot described
Receives: Drug: Simvastatin
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to confirmed disability progression between simvastatin and placebo arm based on change in EDSS scores compared to baseline.

    The initial disability progression event is finalised as positive if disability is sustained and confirmed ≥6* months later. Progression of disability defined as an increase of at least 1 point if EDSS baseline score \<6, or an increase of 0.5 point if baseline EDSS score is ≥6.

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54

Secondary outcomes (15)

  1. Response rate on the patient reported outcome form Multiple Sclerosis Walking Scale-12 version 2 (MSWS-12v2)

    MSWS-12v2 is a12 item patient report measure on the impact of MS on the individual's walking ability over the previous 2 weeks. Each item will be summed to generate a total score and transformed to a scale with a range of 0 to 100 with high scores indicating greater impact on walking.

    Measured: Annually - baseline, month 12, 24 and 36

  2. Response rate on the patient reported outcome form Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2)

    MS Impact Scale-29 version 2 (MSIS-29v2) - A psychometrically validated patient-reported outcome measure increasingly used for measuring the impact of MS on people's lives. The 29-item scale assesses the impact of MS on people's health related quality of life in terms of their physical and psychological well-being over the previous 2 weeks.

    Measured: Annually - baseline, month 12, 24 and 36

  3. Cost effectiveness of intervention

    To estimate the incremental cost and cost-effectiveness of simvastatin versus standard care for the trial period and for the lifetime horizon using the Client Client Services Receipt Inventory Form.

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36

  4. Evaluating change in degree of disability based on the modified Rankin scale (mRS)

    mRS is used to evaluate the degree of disability in daily activities of those with neurological disability.

    Measured: Annually - baseline, month 12, 24 and 36

  5. Change in visual function based on the Sloan Low Contrast Visual Acuity (SLCVA)

    Sloan chart testing is a reliable, quantitative, and clinically practical measure of visual function that will be administered by trained assessors. The chart consists of rows of grey letters on a white background. Letters are displayed in decreasing order from the top of the chart to the bottom. Testing will be conducted at three different contrast levels (100%, 2.5% and 1.25%). The chart will be scored based on the number of letters correctly identified out of 60.

    Measured: Annually - baseline, month 12, 24 and 36

  6. Difference in patient reported quality of life based on the EuroQoL Health Related Quality of Life - 5 Dimensions - 5 Levels (EQ-5D 5L) scores

    EQ-5D 5L is a 5 item questionnaire (assessing - mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and visual analogue scale (VAS) enables calculation of quality adjusted life years (QALY) to enable health economic analyses to be performed. Each dimension assessed has 5 response scales to select from: no problems, slight problems, moderate problems, severe problems, and extreme problems

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36

  7. Change in a modified Multiple Sclerosis Functional Composite scores

    A Modified Multiple Sclerosis Functional Composite (MSFC) score comprised of 3 components (T25FW, 9HPT, SDMT). The Symbol digit modalities test (SDMT) will replace the Paced Auditory Serial Addition Test (PASAT), one of the three components in the Standard MSFC.

    Measured: Annually - baseline, month 12, 24 and 36

  8. Change in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

    BICAMS is a composite cognitive assessment tool comprising of the three components : Symbol Digit Modalities Test (SDMT) , California Verbal Learning Test-II (CVLT-II) and Brief visuospatial memory test- Revised (BVMT-R)

    Measured: Baseline and month 36

  9. Change in cognitive impairment based on Symbol Digit Modalities Test (SDMT) scores

    SDMT is a brief measure of cognitive processing speed. It measures information processing speed for visually presented stimuli, but is self-paced, with at least equal reliability and sensitivity to the presence of worsening cognitive impairment.

    Measured: Annually - baseline, month 12, 24 and 36

  10. Change in fatigue as measured by the Chalder Fatigue Scale

    A questionnaire measuring the severity of physical and mental fatigue. The total score range is minimum of 0 and maximum of 33.

    For the subscales, physical fatigue score has a minimum of 0 and maximum of 21. The Mental fatigue score has a minimum of 0 and maximum of 12.

    Measured: Annually - baseline, month 12, 24 and 36

  11. Change in rates of service utilisation as measured by the Client Service Receipt Inventory (CSRI) questionnaire

    The CSRI is a questionnaire that collects information on service utilisation, income, accommodation and other cost-related variables. Its primary purpose is to allow resource use patterns in each of the two arms to be described, and support costs to be estimated for health economics purposes.

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36

  12. Change in time taken to complete 25-Foot Timed Walk (T25FW)

    T25-FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54

  13. Difference in the number and severity of multiple sclerosis related relapse events between treatment groups

    A relapse will be defined as new or worsening neurological symptom(s) in the absence of fever, lasting for more than 24 hours, and have been preceded by a period of clinical stability of at least 30 days, with no other explanation than MS.

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54

  14. Evaluating the time to disability progression based on a secondary composite progression outcome measure

    A secondary composite progression outcome measure defined as one or more of: ≥20% increase in time taken to complete the 25 Foot Walk (T25FW); or ≥20% increase in time to complete 9 Hole Peg Test (9HPT); or increase in EDSS (0.5 point increase if baseline ≥6 /1.0 point increase if baseline \<6). The initial disability progression event will be finalised as positive if it is sustained and confirmed ≥6 months later*. The time to event analysis will be from randomisation until date of the initial disability progression (if subsequently confirmed)

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54

  15. Change in time taken to complete 9 hole peg test (9HPT)

    The 9HPT is a brief, standardized, quantitative test of upper extremity function. Participants are instructed to pick up 9 pegs, one at a time, as quickly as possible and are required to insert them into 9 empty peg holes. Once all nine pegs have been inserted, the participant should immediately remove the pegs, one at a time. The total time taken to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand. The two trials for each hand are averaged.

    Measured: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jan 2018
  2. Study start28 Mar 2018
  3. Primary completion26 Jul 2024
  4. Study completion25 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
964 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03387670
Sponsor's protocol ID
17/0158
Other IDs
2017-003328-56, 2017
Acronym
MS-STAT2
Status last verified
Sep 2024
First submitted
28 Nov 2017
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chataway J, Williams T, Blackstone J, John N, Braisher M, De Angelis F, Bianchi A, Calvi A, Doshi A, Apap Mangion S, Wade C, Bordea E, Merry R, Barton G, Lyle D, Jarman E, Mahad D, Shehu A, Arun T, McDonnell G, Geraldes R, Craner M, Hillier C, Ganesalingam J, Fisniku L, Hobart J, Spilker C, Robertson NP, Kalra S, Pluchino S, Harikrishnan S, Mattoscio M, Harrower T, Young C, Lee M, Chhetri SK, Ahmed F, Rog D, Silber E, Gallagher P, Duddy M, Straukiene A, Nicholas R, Rice C, Tebbs S, Hawton A, Hunter R, Giovannoni G, Ciccarelli O, Beveridge J, Nixon S, Thompson AJ, Greenwood J, Pearson OR, Evangelou N, Sharrack B, Galea I, Gray E, Pavitt S, Chandran S, Ford HL, Frost C, Nicholas JM; MS-STAT2 Investigators. Effect of repurposed simvastatin on disability progression in secondary progressive multiple sclerosis (MS-STAT2): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2025 Oct 11;406(10512):1611-1624. doi: 10.1016/S0140-6736(25)01039-6. Epub 2025 Oct 1.

    PubMed 41045938

  • Blackstone J, Williams T, Nicholas JM, Bordea E, De Angelis F, Bianchi A, Calvi A, Doshi A, John N, Apap Mangion S, Wade C, Merry R, Barton G, Lyle D, Jarman E, Mahad D, Shehu A, Arun T, McDonnell G, Geraldes R, Craner M, Hillier C, Ganesalingam J, Fisniku L, Hobart J, Spilker C, Robertson N, Kalra S, Pluchino S, Harikrishnan S, Mattoscio M, Harrower T, Young C, Lee M, Chhetri S, Ahmed F, Rog D, Silber E, Gallagher P, Duddy M, Straukiene A, Nicholas R, Rice C, Nixon SJ, Beveridge J, Hawton A, Tebbs S, Braisher M, Giovannoni G, Ciccarelli O, Greenwood J, Thompson AJ, Hunter R, Pavitt S, Pearson O, Evangelou N, Sharrack B, Galea I, Chandran S, Ford HL, Frost C, Chataway J. 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. BMJ Open. 2024 Sep 16;14(9):e086414. doi: 10.1136/bmjopen-2024-086414.

    PubMed 39284697

  • Williams T, John N, Calvi A, Bianchi A, De Angelis F, Doshi A, Wright S, Shatila M, Yiannakas MC, Chowdhury F, Stutters J, Ricciardi A, Prados F, MacManus D, Braisher M, Blackstone J, Ciccarelli O, Gandini Wheeler-Kingshott CAM, Barkhof F, Chataway J; UCL MS-STAT2 investigators. Cardiovascular risk factors in secondary progressive multiple sclerosis: A cross-sectional analysis from the MS-STAT2 randomized controlled trial. Eur J Neurol. 2023 Sep;30(9):2769-2780. doi: 10.1111/ene.15924. Epub 2023 Jun 23.

    PubMed 37318885

  • Williams T, Tur C, Eshaghi A, Doshi A, Chan D, Binks S, Wellington H, Heslegrave A, Zetterberg H, Chataway J. Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial. Mult Scler. 2022 Oct;28(12):1913-1926. doi: 10.1177/13524585221114441. Epub 2022 Aug 9.

    PubMed 35946107

  • Williams T, Alexander S, Blackstone J, De Angelis F, John N, Doshi A, Beveridge J, Braisher M, Gray E, Chataway J; MS-SMART and MS-STAT2 Investigators. Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials. Trials. 2022 Aug 9;23(1):644. doi: 10.1186/s13063-022-06588-z.

    PubMed 35945550

  • Williams TE, Holdsworth KP, Nicholas JM, Eshaghi A, Katsanouli T, Wellington H, Heslegrave A, Zetterberg H, Frost C, Chataway J. Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial. Neurol Neuroimmunol Neuroinflamm. 2022 Jan 14;9(2):e1130. doi: 10.1212/NXI.0000000000001130. Print 2022 Mar.

    PubMed 35031587

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Simvastatin in people with Secondary Progressive Multiple Sclerosis (SPMS), run by University College, London at 31 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to confirmed disability progression between simvastatin and placebo arm based on change in EDSS scores compared to baseline. (time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03387670, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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