Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis (MS-STAT)
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|ClinicalTrials.gov Identifier: NCT00647348|
Recruitment Status : Completed
First Posted : March 31, 2008
Results First Posted : December 12, 2019
Last Update Posted : December 12, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Secondary Progressive Multiple Sclerosis||Drug: Simvastatin Drug: Placebo||Phase 2|
The study has now completed see Primary publication:
Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.
Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CR, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas R.
Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||140 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||RCT|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||over-encapsulation of IMP|
|Official Title:||A Phase II Randomised, Placebo-controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.|
|Actual Study Start Date :||January 2008|
|Actual Primary Completion Date :||November 2011|
|Actual Study Completion Date :||November 2011|
Active Comparator: 1
Simvastatin 80mg OD
80mg simvastatin oral once daily for 24 months
Placebo Comparator: 2
Oral placebo tablet once daily for 24 months
- Percentage Change in Whole Brain Volume [ Time Frame: 24 months ]
- Evaluation of Disability (EDSS). [ Time Frame: 24 months ]Score (0 to 10), lower score less disability and better progression. For EDSS, mean score at 24 months was compared between treatment groups using an ANCOVA model adjusting for baseline score and minimisation variables.
- Evaluation of Disability (MSFC Z Score). [ Time Frame: 24 months ]Negative value implies worsening and a positive value implies improvement.
- Evaluation of Disability (MSFC Walk). [ Time Frame: 24 months ]The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark.
- Evaluation of Disability (MSFC Peg Test). [ Time Frame: 24 months ]The patient is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the patient picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded.
- Evaluation of Disability (MSFC PASAT). [ Time Frame: 24 months ]The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. Shorter inter-stimulus intervals, e.g., 2 seconds or less have also been used with the PASAT but tend to increase the difficulty of the task. Score 0 to 60, higher score less disability.
- Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score) [ Time Frame: 24 months ]The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales is scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates a greater impact of the disease on daily function (worse health).
- Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score) [ Time Frame: 24 months ]The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health).
- Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score) [ Time Frame: 24 months ]The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales is scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates a greater impact of the disease on daily function (worse health).
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|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients must have a confirmed diagnosis of multiple sclerosis and at randomisation 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 one point on the EDSS or clinical documentation of increasing disability.
- EDSS 4.0 - 6.5 inclusive
- Women of childbearing age will be required to use appropriate methods of contraception to avoid the unlikely teratogenic effects of simvastatin.
- Able to give written informed consent
- 18 - 65 years
- Unable to give informed consent
- Primary progressive MS
- Those that have experienced a relapse or have been treated with steroids (both i.v. and oral) within 3 months of the screening 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.
- Patient is already taking or is anticipated to be taking a statin.
- Any medications that unfavourably interact with statins: fibrates, nicotinic acid, cyclosporine, azole anti-fungal preparations, macrolideantibiotics, protease inhibitors, nefazodone, verapamil, amiodarone, large amounts of grapefruit juice or alcohol abuse.
- The use of immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) or disease modifying treatments (avonex, rebif, betaferon, glatiramer) within the previous 6 months.
- The use of mitoxantrone if treated within the last 12 months.
- If the patient has ever been treated with alemtuzumab.
- If screening levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatine kinase (CK) are three times the upper limit of normal patients should be excluded.
- Patient unable to tolerate baseline scan or scan not of adequate quality for analysis (e.g. too much movement artefact).
- If a female patient is pregnant or breast feeding
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00647348
|MRI Unit, National Society for Epilepsy, Chesham Lane|
|Chalfont St. Peter, Buckinghamshire, United Kingdom, SL9 0RJ|
|Charing Cross Hospital, Fulham Palace Road|
|Hammersmith, London, United Kingdom, W6 8RF|
|Brighton & Sussex University Hospitals NHS Trust, Eastern Road|
|Brighton, United Kingdom, BN2 5BE|
|Principal Investigator:||Jeremy Chataway, MB BCh, PhD||Imperial College London|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Imperial College London|
|Other Study ID Numbers:||
MREC: 07/Q1602/73 ( Other Identifier: MREC )
2006-006347-31 ( EudraCT Number )
|First Posted:||March 31, 2008 Key Record Dates|
|Results First Posted:||December 12, 2019|
|Last Update Posted:||December 12, 2019|
|Last Verified:||November 2019|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||We are still analysing post-hoc data. The International Progressive MS Alliance have access to some of the data.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
|Time Frame:||next 2 years|
|Access Criteria:||via the CI|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
Secondary progressive Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
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Molecular Mechanisms of Pharmacological Action
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