Back to resultsInvestigation of Simvastatin in Secondary Progressive Multiple Sclerosis (MS-STAT)
Primary Purpose
Secondary Progressive Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Simvastatin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Secondary Progressive Multiple Sclerosis focused on measuring Secondary progressive Multiple Sclerosis, Simvastatin, MRI
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- MRI Unit, National Society for Epilepsy, Chesham Lane
- Charing Cross Hospital, Fulham Palace Road
- Brighton & Sussex University Hospitals NHS Trust, Eastern Road
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
Simvastatin 80mg OD
Placebo
Outcomes
Primary Outcome Measures
Percentage Change in Whole Brain Volume
Secondary Outcome Measures
Evaluation of Disability (EDSS).
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).
Negative value implies worsening and a positive value implies improvement.
Evaluation of Disability (MSFC Walk).
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).
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).
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)
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)
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)
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).
Full Information
NCT ID
NCT00647348
First Posted
March 26, 2008
Last Updated
November 21, 2019
Sponsor
Imperial College London
1. Study Identification
Unique Protocol Identification Number
NCT00647348
Brief Title
Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
Acronym
MS-STAT
Official Title
A Phase II Randomised, Placebo-controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
January 2008 (Actual)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
November 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To determine whether simvastatin at a dose of 80mg can reduce the rate of whole brain atrophy, as measured by MRI, over a 2-year time-period when compared to placebo.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Progressive Multiple Sclerosis
Keywords
Secondary progressive Multiple Sclerosis, Simvastatin, MRI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
RCT
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
over-encapsulation of IMP
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Simvastatin 80mg OD
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
80mg simvastatin oral once daily for 24 months
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral placebo tablet once daily for 24 months
Primary Outcome Measure Information:
Title
Percentage Change in Whole Brain Volume
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Evaluation of Disability (EDSS).
Description
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.
Time Frame
24 months
Title
Evaluation of Disability (MSFC Z Score).
Description
Negative value implies worsening and a positive value implies improvement.
Time Frame
24 months
Title
Evaluation of Disability (MSFC Walk).
Description
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.
Time Frame
24 months
Title
Evaluation of Disability (MSFC Peg Test).
Description
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.
Time Frame
24 months
Title
Evaluation of Disability (MSFC PASAT).
Description
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.
Time Frame
24 months
Title
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score)
Description
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).
Time Frame
24 months
Title
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score)
Description
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).
Time Frame
24 months
Title
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score)
Description
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).
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Chataway, MB BCh, PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
MRI Unit, National Society for Epilepsy, Chesham Lane
City
Chalfont St. Peter
State/Province
Buckinghamshire
ZIP/Postal Code
SL9 0RJ
Country
United Kingdom
Facility Name
Charing Cross Hospital, Fulham Palace Road
City
Hammersmith
State/Province
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Brighton & Sussex University Hospitals NHS Trust, Eastern Road
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We are still analysing post-hoc data. The International Progressive MS Alliance have access to some of the data.
IPD Sharing Time Frame
next 2 years
IPD Sharing Access Criteria
via the CI
Citations:
PubMed Identifier
28600189
Citation
Chan D, Binks S, Nicholas JM, Frost C, Cardoso MJ, Ourselin S, Wilkie D, Nicholas R, Chataway J. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol. 2017 Aug;16(8):591-600. doi: 10.1016/S1474-4422(17)30113-8. Epub 2017 Jun 7.
Results Reference
result
PubMed Identifier
24655729
Citation
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. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.
Results Reference
result
PubMed Identifier
35031587
Citation
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.
Results Reference
derived
Learn more about this trial
Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
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