MS-OPT Version 1.0 dated 12/10/17
Research type
Research Study
Full title
A double-blind, randomised, placebo-controlled single-site study of high dose simvastatin treatment for secondary progressive multiple sclerosis: impact on vascular perfusion and oxidative damage\n
IRAS ID
211212
Contact name
Richard Nicholas
Contact email
Sponsor organisation
University College London
Eudract number
2017-003008-30
Duration of Study in the UK
1 years, 5 months, 0 days
Research summary
Research summary - It is now widely recognised that statins have anti-inflammatory properties that operate independently of their cholesterol lowering effect. In an earlier study looking at Simvastatin in SPMS, we discovered that Simvastatin reduced brain atrophy (volume) and improved a number of disability scores, suggesting that it is neuro-protective, among other findings. We are trying to understand in more detail how the simvastatin was working and in order to find this out we need to conduct a short clinical trial in patients with secondary progressive multiple sclerosis. The new trial proposed will include an additional component of retinal imaging in addition to MRI scans, among other assessments discussed elsewhere in this application.
Lay Summary - A total of forty people with progressive multiple sclerosis took part in this study. Of these, twelve had primary progressive MS and twenty-eight had secondary progressive MS. Participants were randomly assigned to receive either simvastatin (80 mg) or a placebo (a dummy pill) for sixteen weeks.People in both groups were similar in terms of age, education, and disease characteristics. In the simvastatin group, the average age was about 55 years, and participants had been living with MS for around 22 years on average. In the placebo group, the average age was about 53 years, with an average disease duration of 16 years. Around two-thirds of participants in each group were men, and most identified as White British or Caucasian. Many participants had other medical conditions and were taking other medications, but these were balanced across both groups. Overall, there were no major differences between the two groups at the start of the study.
Participants in the simvastatin group began taking 40 milligrams of the drug daily, which was increased to 80 milligrams after 4 weeks if all safety checks were normal. Everyone in this group reached the full dose. In the placebo group, two participants stopped because of side effects, and one withdrew for personal reasons. Most others took their treatment as instructed. People in the simvastatin group missed fewer doses on average than those in the placebo group. Some minor issues occurred during the study, such as missed blood tests, lost medication diaries, or visits done remotely during the COVID-19 pandemic, but none affected participant safety or the overall results.
Overall, simvastatin did not lead to significant improvements in brain MRI results, disability scores, or other main outcomes compared with placebo. There were small, non-significant trends suggesting slightly higher blood flow in some brain regions among those taking simvastatin, but the differences were not large enough to be meaningful. However, one notable positive finding was a significant reduction in oxidative stress, the damage caused by harmful molecules in the body, in the simvastatin group. This was shown by a drop in specific blood markers of oxidative stress, while these markers increased in the placebo group. In contrast, simvastatin was linked to a decrease in blood flow velocity in the retina, while blood flow increased slightly in the placebo group.
In conclusion, simvastatin did not significantly change brain structure, blood flow, or physical disability in people with progressive multiple sclerosis over 16 weeks. However, it did appear to reduce oxidative stress, suggesting that the drug might have some protective biological effects at the molecular level. Further research is needed to understand whether these biological changes could lead to meaningful clinical benefits over a longer period.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
17/LO/2088
Date of REC Opinion
31 Jan 2018
REC opinion
Further Information Favourable Opinion