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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00647348
Recruitment Status : Completed
First Posted : March 31, 2008
Results First Posted : December 12, 2019
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
Imperial College London

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 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.

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

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

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. Percentage Change in Whole Brain Volume [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Evaluation of Disability (EDSS). [ Time Frame: 24 months ]
    Score (0 to 10), lower score less disability and better progression. For EDSS, mean score at 24 months was compared between treatment groups using an ANCOVA model adjusting for baseline score and minimisation variables.

  2. Evaluation of Disability (MSFC Z Score). [ Time Frame: 24 months ]
    Negative value implies worsening and a positive value implies improvement.

  3. Evaluation of Disability (MSFC Walk). [ Time Frame: 24 months ]
    The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark.

  4. Evaluation of Disability (MSFC Peg Test). [ Time Frame: 24 months ]
    The patient is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the patient picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded.

  5. Evaluation of Disability (MSFC PASAT). [ Time Frame: 24 months ]
    The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. Shorter inter-stimulus intervals, e.g., 2 seconds or less have also been used with the PASAT but tend to increase the difficulty of the task. Score 0 to 60, higher score less disability.

  6. Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score) [ Time Frame: 24 months ]
    The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales is scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates a greater impact of the disease on daily function (worse health).

  7. Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score) [ Time Frame: 24 months ]
    The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health).

  8. Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score) [ Time Frame: 24 months ]
    The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5"extremely". Each of the two scales is scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates a greater impact of the disease on daily function (worse health).


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older 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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00647348


Locations
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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
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Principal Investigator: Jeremy Chataway, MB BCh, PhD Imperial College London
More Information
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Publications of Results:

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

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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00647348    
Other Study ID Numbers: MSTC-001
MREC: 07/Q1602/73 ( Other Identifier: MREC )
2006-006347-31 ( EudraCT Number )
First Posted: March 31, 2008    Key Record Dates
Results First Posted: December 12, 2019
Last Update Posted: December 12, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: We are still analysing post-hoc data. The International Progressive MS Alliance have access to some of the data.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: next 2 years
Access Criteria: via the CI

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Imperial College London:
Secondary progressive Multiple Sclerosis
Simvastatin
MRI
Additional relevant MeSH terms:
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Neoplasm Metastasis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
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