A Phase 3 interventional study of Simvastatin and Placebo in Secondary Progressive Multiple Sclerosis (SPMS), sponsored by University College, London. Completed at 31 sites in United Kingdom. Open to participants aged 25 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by University College, London · Phase 3, Interventional, and Treatment
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.
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.
244 studies on the registry are indexed under Multiple Sclerosis, Chronic Progressive; 53 are open to participants now.
This study's enrollment of 964 is above the median of 54 across 189 interventional studies indexed under Multiple Sclerosis, Chronic Progressive.
Browse Multiple Sclerosis, Chronic Progressive studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Simvastatin
Drug: Placebo
* 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
* 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
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.
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54
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.
Time frame: Annually - baseline, month 12, 24 and 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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.
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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)
Time frame: Baseline and month 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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.
Time frame: Annually - baseline, month 12, 24 and 36
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.
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36
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
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54
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.
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54
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)
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54
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.
Time frame: 6 monthly - baseline, month 6, 12, 18, 24, 30, 36, 42, 48, 54
Plan to share: No
Ran from Mar 2018 to primary completion in Jul 2024, 75 months.
Of 20 phase 3 interventional studies under Multiple Sclerosis, Chronic Progressive, half reached primary completion within 61 months of starting (the median), counting those still running; a quarter within 52 and three quarters within 83. This study's 75 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Simvastatin
Multiple Sclerosis, Chronic Progressive →