Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
Condition: Secondary Progressive Multiple Sclerosis
MeSH terms: Neoplasm Metastasis; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
Intervention: Simvastatin; Placebo
Intervention description: 80mg simvastatin oral once daily for 24 months; Oral placebo tablet once daily for 24 months
Intervention MeSH terms: Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: RCT
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: over-encapsulation of IMP
Enrollment: 140.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Secondary progressive Multiple Sclerosis; Simvastatin; MRI

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.
    

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