Trial Outcomes & Findings for Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis (NCT NCT00647348)
NCT ID: NCT00647348
Last Updated: 2019-12-12
Results Overview
COMPLETED
PHASE2
140 participants
24 months
2019-12-12
Participant Flow
Participant milestones
| Measure |
Simvastatin 80mg OD
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Overall Study
STARTED
|
70
|
70
|
|
Overall Study
COMPLETED
|
67
|
64
|
|
Overall Study
NOT COMPLETED
|
3
|
6
|
Reasons for withdrawal
| Measure |
Simvastatin 80mg OD
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
6
|
Baseline Characteristics
Investigation of Simvastatin in Secondary Progressive Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Simvastatin 80mg OD
n=70 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=70 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
Total
n=140 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
51.5 years
STANDARD_DEVIATION 7.0 • n=5 Participants
|
51.1 years
STANDARD_DEVIATION 6.8 • n=7 Participants
|
51.3 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
49 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
69 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
70 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
140 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: 1 participant had a missing data
Outcome measures
| Measure |
Simvastatin 80mg OD
n=66 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=64 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Percentage Change in Whole Brain Volume
|
0.288 percentage of brain volumen change
Standard Deviation 0.521
|
0.584 percentage of brain volumen change
Standard Deviation 0.498
|
SECONDARY outcome
Timeframe: 24 monthsScore (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.
Outcome measures
| Measure |
Simvastatin 80mg OD
n=67 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=61 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Evaluation of Disability (EDSS).
|
5.93 score on a scale
Standard Deviation 1.11
|
6.35 score on a scale
Standard Deviation 0.83
|
SECONDARY outcome
Timeframe: 24 monthsNegative value implies worsening and a positive value implies improvement.
Outcome measures
| Measure |
Simvastatin 80mg OD
n=58 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=49 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Evaluation of Disability (MSFC Z Score).
|
-0.78 score on a scale
Standard Deviation 2.06
|
-1.21 score on a scale
Standard Deviation 2.59
|
SECONDARY outcome
Timeframe: 24 monthsThe 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.
Outcome measures
| Measure |
Simvastatin 80mg OD
n=62 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=54 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Evaluation of Disability (MSFC Walk).
|
1.83 foot per second
Standard Deviation 1.61
|
1.55 foot per second
Standard Deviation 1.19
|
SECONDARY outcome
Timeframe: 24 monthsThe 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.
Outcome measures
| Measure |
Simvastatin 80mg OD
n=61 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=54 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Evaluation of Disability (MSFC Peg Test).
|
0.033 speed per second
Standard Deviation 0.010
|
0.033 speed per second
Standard Deviation 0.010
|
SECONDARY outcome
Timeframe: 24 monthsThe 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.
Outcome measures
| Measure |
Simvastatin 80mg OD
n=61 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=50 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Evaluation of Disability (MSFC PASAT).
|
38.3 score on a scale
Standard Deviation 15.4
|
35.2 score on a scale
Standard Deviation 18.0
|
SECONDARY outcome
Timeframe: 24 monthsThe 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).
Outcome measures
| Measure |
Simvastatin 80mg OD
n=66 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=57 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Total Score)
|
70.1 score on a scale
Standard Deviation 15.6
|
76.1 score on a scale
Standard Deviation 16.3
|
SECONDARY outcome
Timeframe: 24 monthsThe 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).
Outcome measures
| Measure |
Simvastatin 80mg OD
n=66 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=57 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Physical Score)
|
51.7 score on a scale
Standard Deviation 11.4
|
56.3 score on a scale
Standard Deviation 11.8
|
SECONDARY outcome
Timeframe: 24 monthsThe 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).
Outcome measures
| Measure |
Simvastatin 80mg OD
n=66 Participants
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=57 Participants
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Disease Impact Specific to the Disease and Rated by the Patient (MSIS-29 Questionnaire Psychological Score)
|
18.3 score on a scale
Standard Deviation 5.8
|
19.8 score on a scale
Standard Deviation 6.0
|
Adverse Events
Simvastatin 80mg OD
Placebo
Serious adverse events
| Measure |
Simvastatin 80mg OD
n=70 participants at risk
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=70 participants at risk
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Immune system disorders
Grade 3 relapse (requiring hospital admission)
|
4.3%
3/70 • Collected over 24 months
|
7.1%
5/70 • Collected over 24 months
|
|
Gastrointestinal disorders
Abdominal Lesion Biopsy
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Gastrointestinal disorders
Appendectomy
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Psychiatric disorders
Depression
|
1.4%
1/70 • Collected over 24 months
|
0.00%
0/70 • Collected over 24 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Injury, poisoning and procedural complications
Fracture
|
1.4%
1/70 • Collected over 24 months
|
2.9%
2/70 • Collected over 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
1.4%
1/70 • Collected over 24 months
|
0.00%
0/70 • Collected over 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Nervous system disorders
Seizures
|
1.4%
1/70 • Collected over 24 months
|
0.00%
0/70 • Collected over 24 months
|
|
Nervous system disorders
Increased spasticity
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Nervous system disorders
Sub-arachnoid haemorrhage
|
0.00%
0/70 • Collected over 24 months
|
1.4%
1/70 • Collected over 24 months
|
|
Renal and urinary disorders
Urinary tract infection
|
2.9%
2/70 • Collected over 24 months
|
4.3%
3/70 • Collected over 24 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
2.9%
2/70 • Collected over 24 months
|
0.00%
0/70 • Collected over 24 months
|
|
Nervous system disorders
Viral encephalitis
|
1.4%
1/70 • Collected over 24 months
|
0.00%
0/70 • Collected over 24 months
|
Other adverse events
| Measure |
Simvastatin 80mg OD
n=70 participants at risk
Simvastatin: 80mg simvastatin oral once daily for 24 months
|
Placebo
n=70 participants at risk
Placebo: Oral placebo tablet once daily for 24 months
|
|---|---|---|
|
Nervous system disorders
Relapse
|
24.3%
17/70 • Collected over 24 months
|
24.3%
17/70 • Collected over 24 months
|
|
Nervous system disorders
cramp
|
17.1%
12/70 • Collected over 24 months
|
14.3%
10/70 • Collected over 24 months
|
|
Musculoskeletal and connective tissue disorders
headache
|
4.3%
3/70 • Collected over 24 months
|
14.3%
10/70 • Collected over 24 months
|
|
General disorders
pain
|
10.0%
7/70 • Collected over 24 months
|
18.6%
13/70 • Collected over 24 months
|
|
Nervous system disorders
worsening mobility
|
12.9%
9/70 • Collected over 24 months
|
11.4%
8/70 • Collected over 24 months
|
|
Nervous system disorders
increase spasticity
|
0.00%
0/70 • Collected over 24 months
|
10.0%
7/70 • Collected over 24 months
|
|
Infections and infestations
Urinary infection
|
12.9%
9/70 • Collected over 24 months
|
11.4%
8/70 • Collected over 24 months
|
Additional Information
Professor Jeremy Chataway, Chief Investigator
University of London
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place