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Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis (MS-STAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00647348
Recruitment Status : Completed
First Posted : March 31, 2008
Results First Posted : December 12, 2019
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date  ICMJE March 26, 2008
First Posted Date  ICMJE March 31, 2008
Results First Submitted Date  ICMJE May 1, 2019
Results First Posted Date  ICMJE December 12, 2019
Last Update Posted Date December 12, 2019
Actual Study Start Date  ICMJE January 2008
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
Percentage Change in Whole Brain Volume [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2008)
Quantitative MRI analysis to measure cerebral atrophy, and inflammation. [ Time Frame: Months 12 & 24 ]
Change History Complete list of historical versions of study NCT00647348 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2019)
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2008)
Evaluations of disability (EDSS, MSFC, MSIS-29), quality of life (SF-36), cognitive & behavioural function tests. Immunological assays to determine the pleiotropic effects of simvastatin on immune function. [ Time Frame: Months 12 & 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
Official Title  ICMJE A Phase II Randomised, Placebo-controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
RCT
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
over-encapsulation of IMP
Primary Purpose: Treatment
Condition  ICMJE Secondary Progressive Multiple Sclerosis
Intervention  ICMJE
  • Drug: Simvastatin
    80mg simvastatin oral once daily for 24 months
  • Drug: Placebo
    Oral placebo tablet once daily for 24 months
Study Arms  ICMJE
  • Active Comparator: 1
    Simvastatin 80mg OD
    Intervention: Drug: Simvastatin
  • Placebo Comparator: 2
    Placebo
    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 28, 2008)
140
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2011
Actual Primary Completion Date November 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00647348
Other Study ID Numbers  ICMJE MSTC-001
MREC: 07/Q1602/73 ( Other Identifier: MREC )
2006-006347-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: next 2 years
Access Criteria: via the CI
Responsible Party Imperial College London
Study Sponsor  ICMJE Imperial College London
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jeremy Chataway, MB BCh, PhD Imperial College London
PRS Account Imperial College London
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP