MS-STAT: Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis

Sponsor
Imperial College London (Other)
Overall Status
Completed
CT.gov ID
NCT00647348
Collaborator
(none)
140
3
2
46
46.7
1

Study Details

Study Description

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
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

Study Type:
Interventional
Actual Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
RCTRCT
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 :
Jan 1, 2008
Actual Primary Completion Date :
Nov 1, 2011
Actual Study Completion Date :
Nov 1, 2011

Arms and Interventions

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

Primary Outcome Measures

  1. Percentage Change in Whole Brain Volume [24 months]

Secondary Outcome Measures

  1. Evaluation of Disability (EDSS). [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). [24 months]

    Negative value implies worsening and a positive value implies improvement.

  3. Evaluation of Disability (MSFC Walk). [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). [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). [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) [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) [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) [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

Criteria

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

Locations

Site City State Country Postal Code
1 MRI Unit, National Society for Epilepsy, Chesham Lane Chalfont St. Peter Buckinghamshire United Kingdom SL9 0RJ
2 Charing Cross Hospital, Fulham Palace Road Hammersmith London United Kingdom W6 8RF
3 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00647348
Other Study ID Numbers:
  • MSTC-001
  • MREC: 07/Q1602/73
  • 2006-006347-31
First Posted:
Mar 31, 2008
Last Update Posted:
Dec 12, 2019
Last Verified:
Nov 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
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
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Period Title: Overall Study
STARTED 70 70
COMPLETED 67 64
NOT COMPLETED 3 6

Baseline Characteristics

Arm/Group Title Simvastatin 80mg OD Placebo Total
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months Total of all reporting groups
Overall Participants 70 70 140
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
70
100%
70
100%
140
100%
>=65 years
0
0%
0
0%
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
51.5
(7.0)
51.1
(6.8)
51.3
(6.9)
Sex: Female, Male (Count of Participants)
Female
49
70%
48
68.6%
97
69.3%
Male
21
30%
22
31.4%
43
30.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
1.4%
1
1.4%
2
1.4%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
0
0%
3
4.3%
3
2.1%
White
69
98.6%
63
90%
132
94.3%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
3
4.3%
3
2.1%
Region of Enrollment (Count of Participants)
United Kingdom
70
100%
70
100%
140
100%

Outcome Measures

1. Primary Outcome
Title Percentage Change in Whole Brain Volume
Description
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
1 participant had a missing data
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 66 64
Mean (Standard Deviation) [percentage of brain volumen change]
0.288
(0.521)
0.584
(0.498)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simvastatin 80mg OD, Placebo
Comments
Type of Statistical Test Other
Comments intention-to-treat analysis
Statistical Test of Hypothesis p-Value 0.003
Comments
Method BBSI=brain boundary shift integral
Comments
2. Secondary Outcome
Title Evaluation of Disability (EDSS).
Description 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.
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 67 61
Mean (Standard Deviation) [score on a scale]
5.93
(1.11)
6.35
(0.83)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simvastatin 80mg OD, Placebo
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments EDSS,mean score at 24 months was compared between treatment groups using an ANCOVA model adjusting for baseline score and minimisation variables.
Method ANCOVA
Comments EDSS,mean score at 24 months was compared between treatment groups using an ANCOVA model adjusting for baseline score and minimisation variables.
3. Secondary Outcome
Title Evaluation of Disability (MSFC Z Score).
Description Negative value implies worsening and a positive value implies improvement.
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 58 49
Mean (Standard Deviation) [score on a scale]
-0.78
(2.06)
-1.21
(2.59)
4. Secondary Outcome
Title Evaluation of Disability (MSFC Walk).
Description 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.
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 62 54
Mean (Standard Deviation) [foot per second]
1.83
(1.61)
1.55
(1.19)
5. Secondary Outcome
Title Evaluation of Disability (MSFC Peg Test).
Description 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.
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 61 54
Mean (Standard Deviation) [speed per second]
0.033
(0.010)
0.033
(0.010)
6. Secondary Outcome
Title Evaluation of Disability (MSFC PASAT).
Description 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.
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 61 50
Mean (Standard Deviation) [score on a scale]
38.3
(15.4)
35.2
(18.0)
7. Secondary Outcome
Title Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score)
Description 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).
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 66 57
Mean (Standard Deviation) [score on a scale]
70.1
(15.6)
76.1
(16.3)
8. Secondary Outcome
Title Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score)
Description 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).
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 66 57
Mean (Standard Deviation) [score on a scale]
51.7
(11.4)
56.3
(11.8)
9. Secondary Outcome
Title Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score)
Description 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).
Time Frame 24 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
Measure Participants 66 57
Mean (Standard Deviation) [score on a scale]
18.3
(5.8)
19.8
(6.0)

Adverse Events

Time Frame Collected over 24 months
Adverse Event Reporting Description
Arm/Group Title Simvastatin 80mg OD Placebo
Arm/Group Description Simvastatin: 80mg simvastatin oral once daily for 24 months Placebo: Oral placebo tablet once daily for 24 months
All Cause Mortality
Simvastatin 80mg OD Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/70 (0%) 0/70 (0%)
Serious Adverse Events
Simvastatin 80mg OD Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/70 (12.9%) 14/70 (20%)
Gastrointestinal disorders
Abdominal Lesion Biopsy 0/70 (0%) 1/70 (1.4%)
Appendectomy 0/70 (0%) 1/70 (1.4%)
Immune system disorders
Grade 3 relapse (requiring hospital admission) 3/70 (4.3%) 5/70 (7.1%)
Injury, poisoning and procedural complications
Fall 0/70 (0%) 1/70 (1.4%)
Fracture 1/70 (1.4%) 2/70 (2.9%)
Road traffic accident 0/70 (0%) 1/70 (1.4%)
Nervous system disorders
Seizures 1/70 (1.4%) 0/70 (0%)
Increased spasticity 0/70 (0%) 1/70 (1.4%)
Sub-arachnoid haemorrhage 0/70 (0%) 1/70 (1.4%)
Viral encephalitis 1/70 (1.4%) 0/70 (0%)
Psychiatric disorders
Depression 1/70 (1.4%) 0/70 (0%)
Renal and urinary disorders
Urinary tract infection 2/70 (2.9%) 3/70 (4.3%)
Respiratory, thoracic and mediastinal disorders
Pneumonia 1/70 (1.4%) 0/70 (0%)
Pulmonary embolism 0/70 (0%) 1/70 (1.4%)
Upper respiratory tract infection 2/70 (2.9%) 0/70 (0%)
Other (Not Including Serious) Adverse Events
Simvastatin 80mg OD Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 49/70 (70%) 54/70 (77.1%)
General disorders
pain 7/70 (10%) 13/70 (18.6%)
Infections and infestations
Urinary infection 9/70 (12.9%) 8/70 (11.4%)
Musculoskeletal and connective tissue disorders
headache 3/70 (4.3%) 10/70 (14.3%)
Nervous system disorders
Relapse 17/70 (24.3%) 17/70 (24.3%)
cramp 12/70 (17.1%) 10/70 (14.3%)
worsening mobility 9/70 (12.9%) 8/70 (11.4%)
increase spasticity 0/70 (0%) 7/70 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Professor Jeremy Chataway, Chief Investigator
Organization University of London
Phone 07974752295
Email j.chataway@ucl.ac.uk
Responsible Party:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00647348
Other Study ID Numbers:
  • MSTC-001
  • MREC: 07/Q1602/73
  • 2006-006347-31
First Posted:
Mar 31, 2008
Last Update Posted:
Dec 12, 2019
Last Verified:
Nov 1, 2019