Official Title: “A Phase II Randomised, Placebo-Controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: September 2010

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• Quantitative MRI analysis to measure cerebral atrophy, and inflammation.
  • Time Frame: Months 12 & 24
    Safety Issue?: No

Secondary Measures

• 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
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Imperial College London

Overall Clinical Trial Officials and Contacts

Jeremy Chataway, MB BCh, PhD Principal Investigator Imperial College London  

Overall Contact: David Wilkie, BA, MA 0044 (0) 208 383 0675 d.wilkie@imperial.ac.uk

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00647348

Study ID Number: MSTC-001

ClinicalTrials.gov Identifier: NCT00647348

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency