MS-STAT: Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
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
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
- Percentage Change in Whole Brain Volume [24 months]
Secondary Outcome Measures
- 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.
- Evaluation of Disability (MSFC Z Score). [24 months]
Negative value implies worsening and a positive value implies improvement.
- 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.
- 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.
- 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.
- 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).
- 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).
- 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
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.- MSTC-001
- MREC: 07/Q1602/73
- 2006-006347-31
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
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 |
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. |
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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
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 |
j.chataway@ucl.ac.uk |
- MSTC-001
- MREC: 07/Q1602/73
- 2006-006347-31