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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Secondary Progressive Multiple Sclerosis	Drug: Simvastatin; Drug: Placebo	Phase 2

Detailed Description:

The study has now completed and study data is in the process of being reviewed and correlated.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	140 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase II Randomised, Placebo-controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.
Study Start Date :	January 2008
Actual Primary Completion Date :	November 2011
Actual Study Completion Date :	November 2011

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: 1; Simvastatin 80mg OD	Drug: Simvastatin; 80mg simvastatin oral once daily for 24 months
Placebo Comparator: 2; Placebo	Drug: Placebo; Oral placebo tablet once daily for 24 months

Outcome Measures

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Primary Outcome Measures :

1. Quantitative MRI analysis to measure cerebral atrophy, and inflammation. [ Time Frame: Months 12 & 24 ]

Secondary Outcome Measures :

1. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United Kingdom
MRI Unit, National Society for Epilepsy, Chesham Lane
Chalfont St. Peter, Buckinghamshire, United Kingdom, SL9 0RJ
Charing Cross Hospital, Fulham Palace Road
Hammersmith, London, United Kingdom, W6 8RF
Brighton & Sussex University Hospitals NHS Trust, Eastern Road
Brighton, United Kingdom, BN2 5BE

Sponsors and Collaborators

Imperial College London

Investigators

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Imperial College London
ClinicalTrials.gov Identifier:	NCT00647348 History of Changes
Other Study ID Numbers:	MSTC-001; EudraCT: 2006-006347-31; MREC: 07/Q1602/73
First Posted:	March 31, 2008
Last Update Posted:	November 27, 2012
Last Verified:	November 2012

Keywords provided by Imperial College London:

Secondary progressive Multiple Sclerosis; Simvastatin; MRI

Additional relevant MeSH terms:

Sclerosis; Multiple Sclerosis; Neoplasm Metastasis; Multiple Sclerosis, Chronic Progressive; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases	Neoplastic Processes; Neoplasms; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors