Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis

NCT00647348 | Completed Phase 2 Results DMC

• 3 other identifiers: MSTC-001MREC: 07/Q1602/732006-006347-31
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 3

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.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

Secondary progressive Multiple Sclerosis; Simvastatin; MRI

Outcome Measures

Primary Outcomes (1)

• Percentage Change in Whole Brain Volume

  24 months

Secondary Outcomes (8)

• Evaluation of Disability (EDSS).

  24 months

• Evaluation of Disability (MSFC Z Score).

  24 months

• Evaluation of Disability (MSFC Walk).

  24 months

• Evaluation of Disability (MSFC Peg Test).

  24 months

• Evaluation of Disability (MSFC PASAT).

  24 months

Study Arms (2)

1

ACTIVE COMPARATOR

Simvastatin 80mg OD

Drug: Simvastatin

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Simvastatin DRUG

80mg simvastatin oral once daily for 24 months

1

Placebo DRUG

Oral placebo tablet once daily for 24 months

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years

You may not qualify if:

• 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

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (3)

MRI Unit, National Society for Epilepsy, Chesham Lane

Chalfont Saint Peter, Buckinghamshire, SL9 0RJ, United Kingdom

Location

Charing Cross Hospital, Fulham Palace Road

Hammersmith, London, W6 8RF, United Kingdom

Location

Brighton & Sussex University Hospitals NHS Trust, Eastern Road

Brighton, BN2 5BE, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 28600189 RESULT

• 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.

  PMID: 24655729 RESULT

• 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.

  PMID: 35031587 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Professor Jeremy Chataway, Chief Investigator
• Organization: University of London

j.chataway@ucl.ac.uk

07974752295

Study Officials

• Jeremy Chataway, MB BCh, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: over-encapsulation of IMP
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: RCT

Study Record Dates

• First Submitted: March 26, 2008
• First Posted: March 31, 2008
• Study Start: January 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 12, 2019
• Results First Posted: December 12, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: next 2 years
• Access Criteria: via the CI

Locations

GB (3)