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

• ClinicalTrials.gov Identifier: NCT00647348
• Recruitment Status: Completed
• First Posted: March 31, 2008
• Last Update Posted: November 27, 2012
• Sponsor: Imperial College London
• Information provided by (Responsible Party): Imperial College London

Tracking Information

• First Submitted Date: March 26, 2008
• First Posted Date: March 31, 2008
• Last Update Posted Date: November 27, 2012
• Study Start Date: January 2008
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 28, 2008): Quantitative MRI analysis to measure cerebral atrophy, and inflammation. [ Time Frame: Months 12 & 24 ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT00647348 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures (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 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
• Official Title: 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 and study data is in the process of being reviewed and correlated.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Secondary Progressive Multiple Sclerosis

Intervention

• Drug: Simvastatin
  80mg simvastatin oral once daily for 24 months
• Drug: Placebo
  Oral placebo tablet once daily for 24 months

Study Arms

• Active Comparator: 1
  Simvastatin 80mg OD
  Intervention: Drug: Simvastatin
• Placebo Comparator: 2
  Placebo
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 28, 2008): 140
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 2011
• Actual Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00647348
• Other Study ID Numbers: MSTC-001; EudraCT: 2006-006347-31; MREC: 07/Q1602/73
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Imperial College London
• Study Sponsor: Imperial College London
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jeremy Chataway, MB BCh, PhD; Imperial College London

• PRS Account: Imperial College London
• Verification Date: November 2012