Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis

Condition(s) targeted: Secondary Progressive Multiple Sclerosis

Intervention: Simvastatin (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Imperial College London

Official(s) and/or principal investigator(s):
Jeremy Chataway, MB BCh, PhD, Principal Investigator, Affiliation: Imperial College London

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

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.

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

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

Primary outcome: Quantitative MRI analysis to measure cerebral atrophy, and inflammation.

Secondary outcome: 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

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

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

Brighton & Sussex University Hospitals NHS Trust, Eastern Road, Brighton BN2 5BE, United Kingdom; Not yet recruiting
Dennis Chan, MD, PhD, Principal Investigator

MRI Unit, National Society for Epilepsy, Chesham Lane, Chalfont St. Peter, Buckinghamshire SL9 0RJ, United Kingdom; Not yet recruiting
Jeremy Chataway, MB BCh; PhD, Principal Investigator

Charing Cross Hospital, Fulham Palace Road, Hammersmith, London W6 8RF, United Kingdom; Recruiting
Richard Nicholas, MD, PhD, Principal Investigator

Starting date: January 2008
Ending date: January 2011
Last updated: April 3, 2008