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

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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 Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Secondary Progressive Multiple Sclerosis
Interventions Drug: Simvastatin
Drug: Placebo
Enrollment 140
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Simvastatin 80mg OD Placebo
Hide 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
Reason Not Completed
Lost to Follow-up             3             6
Arm/Group Title Simvastatin 80mg OD Placebo Total
Hide 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 Number of Baseline Participants 70 70 140
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
70
 100.0%
70
 100.0%
140
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 70 participants 70 participants 140 participants
51.5  (7.0) 51.1  (6.8) 51.3  (6.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
Female
49
  70.0%
48
  68.6%
97
  69.3%
Male
21
  30.0%
22
  31.4%
43
  30.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 70 participants 70 participants 140 participants
American Indian or Alaska Native
0
   0.0%
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%
0
   0.0%
Black or African American
0
   0.0%
3
   4.3%
3
   2.1%
White
69
  98.6%
63
  90.0%
132
  94.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
3
   4.3%
3
   2.1%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United Kingdom Number Analyzed 70 participants 70 participants 140 participants
70
 100.0%
70
 100.0%
140
 100.0%
1.Primary Outcome
Title Percentage Change in Whole Brain Volume
Hide Description [Not Specified]
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
1 participant had a missing data
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 66 64
Mean (Standard Deviation)
Unit of Measure: percentage of brain volumen change
0.288  (0.521) 0.584  (0.498)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simvastatin 80mg OD, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments intention-to-treat analysis
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method BBSI=brain boundary shift integral
Comments [Not Specified]
2.Secondary Outcome
Title Evaluation of Disability (EDSS).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 67 61
Mean (Standard Deviation)
Unit of Measure: score on a scale
5.93  (1.11) 6.35  (0.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Simvastatin 80mg OD, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Hide Description Negative value implies worsening and a positive value implies improvement.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 58 49
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.78  (2.06) -1.21  (2.59)
4.Secondary Outcome
Title Evaluation of Disability (MSFC Walk).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 62 54
Mean (Standard Deviation)
Unit of Measure: foot per second
1.83  (1.61) 1.55  (1.19)
5.Secondary Outcome
Title Evaluation of Disability (MSFC Peg Test).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 61 54
Mean (Standard Deviation)
Unit of Measure: speed per second
0.033  (0.010) 0.033  (0.010)
6.Secondary Outcome
Title Evaluation of Disability (MSFC PASAT).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 61 50
Mean (Standard Deviation)
Unit of Measure: 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 66 57
Mean (Standard Deviation)
Unit of Measure: 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 66 57
Mean (Standard Deviation)
Unit of Measure: 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)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Simvastatin 80mg OD Placebo
Hide Arm/Group Description:
Simvastatin: 80mg simvastatin oral once daily for 24 months
Placebo: Oral placebo tablet once daily for 24 months
Overall Number of Participants Analyzed 66 57
Mean (Standard Deviation)
Unit of Measure: score on a scale
18.3  (5.8) 19.8  (6.0)
Time Frame Collected over 24 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Simvastatin 80mg OD Placebo
Hide 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 (%) Affected / at Risk (%)
Total   0/70 (0.00%)   0/70 (0.00%) 
Hide Serious Adverse Events
Simvastatin 80mg OD Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   9/70 (12.86%)   14/70 (20.00%) 
Gastrointestinal disorders     
Abdominal Lesion Biopsy † 1  0/70 (0.00%)  1/70 (1.43%) 
Appendectomy † 1  0/70 (0.00%)  1/70 (1.43%) 
Immune system disorders     
Grade 3 relapse (requiring hospital admission) † 1  3/70 (4.29%)  5/70 (7.14%) 
Injury, poisoning and procedural complications     
Fall † 1  0/70 (0.00%)  1/70 (1.43%) 
Fracture † 1  1/70 (1.43%)  2/70 (2.86%) 
Road traffic accident † 1  0/70 (0.00%)  1/70 (1.43%) 
Nervous system disorders     
Seizures † 1  1/70 (1.43%)  0/70 (0.00%) 
Increased spasticity † 1  0/70 (0.00%)  1/70 (1.43%) 
Sub-arachnoid haemorrhage † 1  0/70 (0.00%)  1/70 (1.43%) 
Viral encephalitis † 1  1/70 (1.43%)  0/70 (0.00%) 
Psychiatric disorders     
Depression † 1  1/70 (1.43%)  0/70 (0.00%) 
Renal and urinary disorders     
Urinary tract infection † 1  2/70 (2.86%)  3/70 (4.29%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia † 1  1/70 (1.43%)  0/70 (0.00%) 
Pulmonary embolism † 1  0/70 (0.00%)  1/70 (1.43%) 
Upper respiratory tract infection † 1  2/70 (2.86%)  0/70 (0.00%) 
1
Term from vocabulary, MedDRA (10.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Simvastatin 80mg OD Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   49/70 (70.00%)   54/70 (77.14%) 
General disorders     
pain † 1 [1]  7/70 (10.00%)  13/70 (18.57%) 
Infections and infestations     
Urinary infection † 1 [2]  9/70 (12.86%)  8/70 (11.43%) 
Musculoskeletal and connective tissue disorders     
headache † 1 [3]  3/70 (4.29%)  10/70 (14.29%) 
Nervous system disorders     
Relapse † 1 [4]  17/70 (24.29%)  17/70 (24.29%) 
cramp † 1 [5]  12/70 (17.14%)  10/70 (14.29%) 
worsening mobility † 1 [6]  9/70 (12.86%)  8/70 (11.43%) 
increase spasticity † 1 [7]  0/70 (0.00%)  7/70 (10.00%) 
1
Term from vocabulary, MedDRA (10.0)
†
Indicates events were collected by systematic assessment
[1]
pain
[2]
UTI
[3]
headache
[4]
relapse of MS
[5]
cramp
[6]
worsening mobility
[7]
spasticity
[Not Specified]
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
Layout table for Results Point of Contact information
Name/Title: Professor Jeremy Chataway, Chief Investigator
Organization: University of London
Phone: 07974752295
EMail: j.chataway@ucl.ac.uk
Publications of Results:
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.
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.
Layout table for additonal information
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 Submitted: March 26, 2008
First Posted: March 31, 2008
Results First Submitted: May 1, 2019
Results First Posted: December 12, 2019
Last Update Posted: December 12, 2019