Clinical trial NCT00647348: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: Secondary progressive Multiple Sclerosis
Simvastatin
MRI
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2008-03-31
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT
Primary purpose: TREATMENT

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 see Primary publication:

Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial.

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.

Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4.

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

Primary outcomes:
measure: Percentage Change in Whole Brain Volume
timeFrame: 24 months
Secondary outcomes:
measure: Evaluation of Disability (EDSS).
timeFrame: 24 months
measure: Evaluation of Disability (MSFC Z Score).
timeFrame: 24 months
measure: Evaluation of Disability (MSFC Walk).
timeFrame: 24 months
measure: Evaluation of Disability (MSFC Peg Test).
timeFrame: 24 months
measure: Evaluation of Disability (MSFC PASAT).
timeFrame: 24 months
measure: Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score)
timeFrame: 24 months
measure: Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score)
timeFrame: 24 months
measure: Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score)
timeFrame: 24 months
Other outcomes:
Locations:
city: Chalfont St. Peter
country: United Kingdom
facility: MRI Unit, National Society for Epilepsy, Chesham Lane
state: Buckinghamshire
city: Hammersmith
country: United Kingdom
facility: Charing Cross Hospital, Fulham Palace Road
state: London
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust, Eastern Road
Study officials:
affiliation: Imperial College London
name: Jeremy Chataway, MB BCh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Williams TE, Holdsworth KP, Nicholas JM, Eshaghi A, Katsanouli T, Wellington H, Heslegrave A, Zetterberg H, Frost C, Chataway J. Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial. Neurol Neuroimmunol Neuroinflamm. 2022 Jan 14;9(2):e1130. doi: 10.1212/NXI.0000000000001130. Print 2022 Mar.