Trial Outcomes & Findings for Simvastatin in Secondary Progressive Multiple Sclerosis (NCT NCT03896217)

Results Overview

To compare patients on simvastatin or placebo using multiple linear regressions. ASL is an MRI method that allows non-invasive measurement of CBF using inversion of arterial water spins as a tracer.The aim is to explore whether subtle changes in CBF occur over time between placebo and simvastatin treated patients, including potential waning of the effects of the drug over time.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

At week 16

Results posted on

2025-07-01

Participant Flow

Participant milestones

Participant milestones
Measure	Simvastatin Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Overall Study STARTED	20	20
Overall Study COMPLETED	19	20
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Forty patients, including 12 primary progressive MS and 28 secondary progressive MS, aged 18-70 years, and presenting with an Expanded Disability Status Scale (EDSS) score 4.0-6.5 were randomly assigned (1:1) to Simvastatin 80 mg or placebo for 16 weeks.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Simvastatin n=20 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Total n=40 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	19 Participants n=5 Participants	18 Participants n=7 Participants	37 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	55.30 Years STANDARD_DEVIATION 7.51 • n=5 Participants • Forty patients, including 12 primary progressive MS and 28 secondary progressive MS, aged 18-70 years, and presenting with an Expanded Disability Status Scale (EDSS) score 4.0-6.5 were randomly assigned (1:1) to Simvastatin 80 mg or placebo for 16 weeks.	52.95 Years STANDARD_DEVIATION 9.48 • n=7 Participants • Forty patients, including 12 primary progressive MS and 28 secondary progressive MS, aged 18-70 years, and presenting with an Expanded Disability Status Scale (EDSS) score 4.0-6.5 were randomly assigned (1:1) to Simvastatin 80 mg or placebo for 16 weeks.	54.13 Years STANDARD_DEVIATION 8.53 • n=5 Participants • Forty patients, including 12 primary progressive MS and 28 secondary progressive MS, aged 18-70 years, and presenting with an Expanded Disability Status Scale (EDSS) score 4.0-6.5 were randomly assigned (1:1) to Simvastatin 80 mg or placebo for 16 weeks.
Sex: Female, Male Female	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	13 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	18 Participants n=7 Participants	38 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Multiple Sclerosis Clinical Phenotype, Categorical Primary Progressive Multiple Sclerosis	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Multiple Sclerosis Clinical Phenotype, Categorical Secondary Progressive Multiple Sclerosis	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: At week 16

Population: Mean percentage of change in CBF from baseline to visit 3 (95%CI)

To compare patients on simvastatin or placebo using multiple linear regressions. ASL is an MRI method that allows non-invasive measurement of CBF using inversion of arterial water spins as a tracer.The aim is to explore whether subtle changes in CBF occur over time between placebo and simvastatin treated patients, including potential waning of the effects of the drug over time.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Effect on Cerebral Blood Flow in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus White Matter	8.55 Percentage of change in CBF Interval -1.63 to 14.77	5.12 Percentage of change in CBF Interval -4.52 to 14.77
Effect on Cerebral Blood Flow in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Gray Matter	5.78 Percentage of change in CBF Interval -2.13 to 13.69	2.06 Percentage of change in CBF Interval -5.43 to 9.54
Effect on Cerebral Blood Flow in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Deep White Matter	8.39 Percentage of change in CBF Interval -2.55 to 19.33	6.69 Percentage of change in CBF Interval -3.67 to 17.05
Effect on Cerebral Blood Flow in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Deep Gray Matter	7.33 Percentage of change in CBF Interval -1.2 to 15.85	2.77 Percentage of change in CBF Interval -5.07 to 10.61
Effect on Cerebral Blood Flow in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Thalamus	4.55 Percentage of change in CBF Interval -5.11 to 14.21	-1.02 Percentage of change in CBF Interval -9.91 to 7.86

PRIMARY outcome

Timeframe: At week 16

Population: Mean percentage of change in ratio Velocity/Vessel Width from baseline to visit 3

To establish if Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) measurements of blood flow are useful correlates for cerebral blood flow measurement on and off treatment.

Outcome measures

Outcome measures
Measure	Simvastatin n=17 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=17 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
AOSLO Measurements of Blood Flow	0.87 percentage of change Interval -15.12 to 16.86	5.89 percentage of change Interval -10.11 to 21.88

SECONDARY outcome

Timeframe: At baseline

Population: Data are reported for ASL CBF at baseline

To evaluate whether ASL is useful correlate for cerebral blood flow measurement on and off treatment.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
MRI: ASL in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus White Matter	27.38 mL/100 g/min Standard Deviation 8.30	25.89 mL/100 g/min Standard Deviation 7.56
MRI: ASL in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Gray Matter	76.82 mL/100 g/min Standard Deviation 18.02	70.78 mL/100 g/min Standard Deviation 15.74
MRI: ASL in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Deep White Matter	24.95 mL/100 g/min Standard Deviation 7.74	23.26 mL/100 g/min Standard Deviation 7.56
MRI: ASL in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Deep Gray Matter	46.33 mL/100 g/min Standard Deviation 11.95	44.72 mL/100 g/min Standard Deviation 11.27
MRI: ASL in White Matter, Gray Matter, Deep White Matter, Deep Gray Matter, and Thalamus Thalamus	54.96 mL/100 g/min Standard Deviation 17.52	51.22 mL/100 g/min Standard Deviation 13.75

SECONDARY outcome

Timeframe: Over 16 weeks

Population: Mean percentage of change from baseline to visit 3

AOSLO of retinal capillary microvessels was applied to calculate retinal perfusion and measure blood flow dynamics at the capillary level. We measured relative venous and artery blood pO2 levels near the optic nerve (central 3 disk diameters) to obtain vessel width and velocity.

Outcome measures

Outcome measures
Measure	Simvastatin n=19 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=18 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
AOSLO Blood Flow Dynamics Vessel width	-3.04 Percentage of change Interval -15.93 to 9.84	-2.64 Percentage of change Interval -14.76 to 9.48
AOSLO Blood Flow Dynamics Velocity	-13.40 Percentage of change Interval -25.5 to 1.29	5.37 Percentage of change Interval -7.1 to 17.84

SECONDARY outcome

Timeframe: At week 16

Population: Mean prcentage of change from baseline to visit 3

To explore whether statin reduce the rate of brain atrophy, including grey matter volumes, on MRI (excluding the effect of pseudo-atrophy, which is a temporary response to the drug rather than an actual loss of tissue). The MRI images will be analysed using softwares developed at UCL to quantify the amount of brain tissue loss over time.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
MRI: Brain Atrophy White Matter	-0.21 Percentage of change Interval -0.79 to 0.36	0.14 Percentage of change Interval -1.17 to 0.46
MRI: Brain Atrophy Gray Matter	-0.32 Percentage of change Interval -0.74 to 0.09	-0.19 Percentage of change Interval -0.58 to 0.2
MRI: Brain Atrophy Cortical Gray Matter	-0.32 Percentage of change Interval -0.75 to 0.1	-0.20 Percentage of change Interval -0.6 to 0.2
MRI: Brain Atrophy Hippocampus	-0.51 Percentage of change Interval -1.11 to 0.09	-0.44 Percentage of change Interval -1.0 to 0.13
MRI: Brain Atrophy Thalamus	-0.25 Percentage of change Interval -0.91 to 0.42	-0.04 Percentage of change Interval -0.67 to 0.59
MRI: Brain Atrophy Pallidum	0.15 Percentage of change Interval -0.79 to 1.09	-0.68 Percentage of change Interval -1.57 to 0.021
MRI: Brain Atrophy Putamen	-0.30 Percentage of change Interval -0.8 to 0.21	-0.85 Percentage of change Interval -1.34 to -0.38
MRI: Brain Atrophy Ventral diencephalon	0.09 Percentage of change Interval -0.48 to 0.66	-0.85 Percentage of change Interval -1.39 to 0.32

SECONDARY outcome

Timeframe: At week 16

Population: Mean percentage of change from baseline to visit 3. Data are reported for white matter

Diffusion weighted imaging (DWI) is an MR imaging technique based upon the measurement of the random Brownian motion of water within a voxel of tissue. This technique has been used to analyse the microstructure of neuronal tissue in particular myelin and axonal integrity.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
MRI: Diffusion Tensor Imaging (DTI) Fractional anisotropy (FA)	-0.01 Percentage of change Interval -0.95 to 0.92	-0.22 Percentage of change Interval -1.14 to 0.69
MRI: Diffusion Tensor Imaging (DTI) Mean diffusivity (MD)	1.13 Percentage of change Interval 0.01 to 2.26	0.31 Percentage of change Interval -0.78 to 1.4

SECONDARY outcome

Timeframe: At week 16

Population: Mean percentage of change from baseline to visit 3. Data are reported for white matter

To assess changes in axonal parameters, such as fiber orientation dispersion and axonal densities occurring over time using NODDI, an advanced MRI technique that reflects the microstructural complexity of dendrites and axons in vivo.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
MRI: Neurite Density and Orientation Dispersion Imaging Intra-neurite volume fraction	-1.27 Percentage of change Interval -2.58 to 0.04	-0.48 Percentage of change Interval -1.75 to 0.79
MRI: Neurite Density and Orientation Dispersion Imaging Isotropic volume fraction	2.45 Percentage of change Interval -0.58 to 5.47	-0.12 Percentage of change Interval -3.06 to 2.83

SECONDARY outcome

Timeframe: At week 16

Population: Mean percentage of change from baseline to visit 3

Macromolecular tissue volume (MTV) is a method of myelin mapping to determine the role of myelin loss or changes in progressive MS. With the macromolecular volume being made up of 50% myelin, we are able to use an in-house analysis pipeline to calculate the MTV - a surrogate marker of brain myelin volume. This metric, alongside diffusion weighted imaging will provide micro-structural detail into the cross-sectional and longitudinal changes occurring in the brain parenchyma of people with progressive MS.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
MRI: MTV Cortical Gray Matter	3.65 Percentage of change Interval -8.29 to 15.59	7.30 Percentage of change Interval -4.3 to 18.89
MRI: MTV Deep Gray Matter	-2.27 Percentage of change Interval -7.31 to 2.77	1.89 Percentage of change Interval -3.01 to 6.79
MRI: MTV Normal-Appearing White Matter	-0.68 Percentage of change Interval -4.72 to 3.36	1.77 Percentage of change Interval -2.15 to 5.7
MRI: MTV Brainstem	-1.69 Percentage of change Interval -7.22 to 3.83	1.71 Percentage of change Interval -3.65 to 7.08
MRI: MTV Lesions	-2.12 Percentage of change Interval -7.79 to 3.56	2.66 Percentage of change Interval -2.86 to 8.17

SECONDARY outcome

Timeframe: At week 16

Population: Mean percentage of change from baseline to visit 3

Inner retinal thickness will be measured using optical coherence tomography (OCT). OCT is a method of retinal imaging which is non-invasive and involves the patient holding their head still and staring at a dim light while imaging takes place. Peripapillary retinal nerve fibre layer (pRNFL) thickness is a strong candidate as a biomarker of axonal degeneration in MS.

Outcome measures

Outcome measures
Measure	Simvastatin n=16 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=18 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
OCT-A: Retinal Nerve Fibre Layer	2.28 Percentage of change Interval -0.08 to 4.64	-0.29 Percentage of change Interval -2.52 to 1.93

SECONDARY outcome

Timeframe: At week 16

Population: Mean percentage of change from baseline to visit 3

OCT-A images will be processed to produce quantitative data of perfusion indices. Vessel density (VD) is defined as the "percentage area occupied by vessels in the segmented area.

Outcome measures

Outcome measures
Measure	Simvastatin n=16 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
OCT-A: Vessel Density	7.59 Percentage of change Interval -11.12 to 26.3	15.15 Percentage of change Interval -1.97 to 32.26

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3

To examine the clinical effect of simvastatin treatment as reported by the clinician. Clinician observed expanded disability status score (EDSS) is a method of quantifying disability in MS and records changes in disability over time. The EDSS scale ranges from 0 (no disability) to 10 (death due to MS) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist and encompasses pyramidal, cerebellar, brainstem, sensory, bowel/bladder function in addition to visual, cerebral and other functions. Changes in score (including no changes) will be recorded to determine progression of disability.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Clinical Outcome: EDSS	-0.19 units on a scale Interval -0.46 to 0.08	0.04 units on a scale Interval -0.21 to 0.3

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3

To examine the clinical effect of simvastatin treatment as reported by the clinician . Multiple Sclerosis Function Composite (MSFC) includes the 25 foot timed foot walk (25TFW), which involves marking a 25-foot distance in an unobstructed hallway; an assistive device (if needed) may be used by the participant and recorded. Their speed is then timed up to a time limit of 3 mins in both directions. Changes in scores will be recorded over the time-points described.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Clinical Outcomes: MSFC: 25 Foot Timed Walk	0.74 Seconds Interval -6.94 to 8.41	2.37 Seconds Interval -4.9 to 9.64

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3

To examine the clinical effect of simvastatin treatment as reported by the clinician. Multiple Sclerosis Function Composite (MSFC) includes the 9 hole peg test (9HPT). The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and non-dominant hands are tested twice (two consecutive trials of the dominant hand, followed immediately by two consecutive trials of the non-dominant hand). It is important that the 9-HPT be administered on a solid table (not a rolling hospital bedside table) and that the 9-HPT apparatus be anchored (e.g., with Dycem). The pegs are selected one at a time, using one hand only, and put into the holes as quickly as possible in any order until all the holes are filled. Then, without pausing, the pegs are removed one at a time and returned to the container. This is timed and recorded at the time-points described.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Clinical Outcomes: MSFC: 9 Hole Peg Test Dominant hand	-0.77 Seconds Interval -13.63 to 12.09	4.51 Seconds Interval -7.65 to 16.68
Clinical Outcomes: MSFC: 9 Hole Peg Test Non-dominant hand	0.78 Seconds Interval -7.66 to 9.22	-0.10 Seconds Interval -8.1 to 7.89

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3.

Symbol Digit Modalities Test (SDMT) is measure of cognitive impairment. The subject is asked to match single digits to symbols using a key as a guide that pairs the numbers to the symbols. They are presented with a page headed by a key that pairs the single digits 1-9 with nine symbols and they then write or orally report their responses in a scoring form. It can be administered in oral and written form and is timed and guided by a trained examiner ie. suitably qualified member of the research team. Changes in scores were recorded over the time-points described. Scores range from 0 to 110, with higher scores indicating better cognitive functioning.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Clinical Outcomes: SDMT	-2.34 Units on a scale Interval -5.94 to 1.25	0.01 Units on a scale Interval -3.4 to 3.42

SECONDARY outcome

Timeframe: At week 20

Population: Mean change from baseline to visit 4

Frontal Assessment Battery (FAB). The FAB is a brief tool that can be used at the bedside or in a clinic setting to assist in discriminating between dementias with a frontal dysexecutive phenotype and dementia of Alzheimer"s Type (DAT). The FAB has validity in distinguishing Fronto-temporal type dementia from DAT in mildly demented patients (MMSE \> 24). Total score is from a maximum of 18, higher scores indicating better performance. Changes in scores were recorded over the time-points described. The FAB evaluates executive functions through six subtests, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Each subtest is scored from 0 to 3, yielding a total score range of 0 to 18. Higher scores indicate better executive functioning. The total score is calculated by summing the six subtest scores.

Outcome measures

Outcome measures
Measure	Simvastatin n=19 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Clinical Outcomes: Frontal Executive Functioning: FAB	0.38 Units on a scale Interval -0.24 to 1.0	0.40 Units on a scale Interval -0.22 to 1.03

SECONDARY outcome

Timeframe: At week 16

Population: Mean change in total score from baseline to visit 3. The FAB evaluates executive functions through six subtests, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. Each subtest is scored from 0 to 3, yielding a total score range of 0 to 18. Higher scores indicate better executive functioning. The total score is calculated by summing the six subtest scores.

To examine the clinical effect of simvastatin treatment as reported by patient reported outcome measures. Patient reported multiple sclerosis impact scale version 2 (MSIS-29v2) is a self-administered questionnaire covering 29 items that asks to what degree MS has impacted the person physically and mentally over the past two weeks. It consists of 29 items divided into two subscales: Physical Impact (20 items; score range: 20-100) and Psychological Impact (9 items; score range: 9-45). Each item is rated on a 5-point Likert scale. Higher scores reflect a greater negative impact of MS on the individual's quality of life.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Patient-Reported Outcomes: MSIS-29v2 Questionnaires. Physical impact	1.08 Units on a scale Interval -4.53 to 6.69	-5.09 Units on a scale Interval -10.39 to 0.2
Patient-Reported Outcomes: MSIS-29v2 Questionnaires. Psychological impact	1.54 Units on a scale Interval -5.11 to 8.19	1.81 Units on a scale Interval -4.48 to 8.1

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3

Patient reported Multiple Sclerosis Walking Test version 2 (MSWT-12V2) is a 12 item self-administered questionnaire that measures walking performance over the previous two weeks. Each items is summed to generate a total score which is then transformed to a scale ranging from 0 to 100. Higher scores indicate greater impact on walking. Changes in scores will be recorded over the time-points described.

Outcome measures

Outcome measures
Measure	Simvastatin n=17 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=19 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Patient-Reported Outcomes: MSWT-12V2 Questionnaires.	1.43 Units on a scale Interval -3.46 to 6.31	3.15 Units on a scale Interval -1.46 to 7.77

SECONDARY outcome

Timeframe: At week 16

Population: Mean change from baseline to visit 3

The EuroQol Health-Related Quality of Life (EQ-5D-5L) is a standardized instrument for assessing health-related quality of life across five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is rated on a five-level scale, ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a visual analogue scale (VAS), on which individuals rate their overall health from 0 (worst imaginable health state) to 100 (best imaginable health state). Results are reported as the mean change in domain scores and VAS ratings from baseline to Visit 3.

Outcome measures

Outcome measures
Measure	Simvastatin n=18 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=20 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Health Economic Outcomes: EQ5D5L Mobility	0.11 Units on a scale Interval -0.09 to 0.32	0.20 Units on a scale Interval 0.001 to 0.39
Health Economic Outcomes: EQ5D5L Self-care	-0.09 Units on a scale Interval -0.39 to 0.2	-0.07 Units on a scale Interval -0.35 to 0.21
Health Economic Outcomes: EQ5D5L Usual activities	0.15 Units on a scale Interval -0.18 to 0.49	0.11 Units on a scale Interval -0.21 to 0.43
Health Economic Outcomes: EQ5D5L Pain/discomfort	0.25 Units on a scale Interval -0.06 to 0.55	0.18 Units on a scale Interval -0.11 to 0.46
Health Economic Outcomes: EQ5D5L Anxiety/depression	-0.08 Units on a scale Interval -0.42 to 0.27	0.07 Units on a scale Interval -0.26 to 0.39
Health Economic Outcomes: EQ5D5L VAS	4.20 Units on a scale Interval -1.41 to 9.81	2.07 Units on a scale Interval -3.25 to 7.39

OTHER_PRE_SPECIFIED outcome

Timeframe: At week 4

Population: Mean percentage of change from baseline to visit 2

Blood samples from these patients will be taken at baseline and at weeks 4, 16 and 20 to investigate the effect of statins on vascular leakage and free radical damage. Biomarkers will be determined as follows: (i) For RNA/DNA oxidative damage serum levels of 8-hydroxyguanosine (8-OHG)/8-hydroxydeoxyguanosine (8-OHdG); (ii) Protein oxidative damage will be determined by assaying plasma proteins for nitrotyrosine and carbonyl content; and (iii) Detection of lipid oxidative damage by assaying for the advanced lipid peroxidation end products 4-hydroxynonenal (4-HNE or HNE), malondialdehyde (MDA), 8-iso-prostaglandin F2α and thiobarbituric acid reactive substances (TBARS) (Miller et al., 2012).

Outcome measures

Outcome measures
Measure	Simvastatin n=15 Participants Simvastatin is part of the pharmacotherapeutic group of HMG-CoA reductase inhibitors (ATC-Code: C10A A01). Simvastatin is licensed within the EU for hypercholesterolemia and cardiovascular prevention but for this trial its use will be outside its licensed indication. The starting dose at baseline was 40 mg of Simvastatin or placebo (one tablet) to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 80 mg (two tablets) if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.	Placebo n=18 Participants Matched placebo taking a dummy pill (Placebo IMP: gelatine tablet with added cellulose microcrystalline). The starting dose at baseline for placebo was 1 tablet to be taken orally in the evening. This was up titrated at Visit 2 (week 4) to 2 tablets if all safety parameters were met at Visit 2. Participants were allocated one bottle each containing 220 tablets for the duration of the study. There was therefore one drug dispensation at baseline, and the patient was reminded to up-titrate after one month at Visit 2.
Exploratory Outcomes: Immune Parameters, and Biomarkers. Nos. Lymph events gated	-381.57 Percentage of change Interval -1151.38 to 388.24	-280.97 Percentage of change Interval -958.49 to 396.55
Exploratory Outcomes: Immune Parameters, and Biomarkers. Nos. CD3+T cell events gated	196.26 Percentage of change Interval -1035.94 to 1428.46	286.48 Percentage of change Interval -798.13 to 1371.09
Exploratory Outcomes: Immune Parameters, and Biomarkers. CD4+ T cells	-113.84 Percentage of change Interval -238.98 to 11.3	13.73 Percentage of change Interval -99.59 to 127.04
Exploratory Outcomes: Immune Parameters, and Biomarkers. CD8+ T cells	-344.68 Percentage of change Interval -615.56 to -73.79	-209.93 Percentage of change Interval -463.84 to 43.98
Exploratory Outcomes: Immune Parameters, and Biomarkers. B cells	-74.50 Percentage of change Interval -464.45 to 315.45	-253.57 Percentage of change Interval -606.9 to 99.74
Exploratory Outcomes: Immune Parameters, and Biomarkers. CD8+ non-T cells	-110.50 Percentage of change Interval -209.31 to 11.69	-41.85 Percentage of change Interval -137.44 to 53.74
Exploratory Outcomes: Immune Parameters, and Biomarkers. CD4+ IFN+ (Th1) cells	-37.60 Percentage of change Interval -672.04 to 596.84	165.81 Percentage of change Interval -425.07 to 756.68
Exploratory Outcomes: Immune Parameters, and Biomarkers. CD4+ IL17+ (Th17) cells	-138.72 Percentage of change Interval -313.51 to 36.06	-71.45 Percentage of change Interval -240.23 to 97.32
Exploratory Outcomes: Immune Parameters, and Biomarkers. 8OH	-24.40 Percentage of change Interval -53.26 to 4.46	26.69 Percentage of change Interval -0.4 to 53.77
Exploratory Outcomes: Immune Parameters, and Biomarkers. Nitro	59.14 Percentage of change Interval 10.4 to 107.87	66.60 Percentage of change Interval 25.78 to 107.42

Adverse Events

Simvastatin

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Prof. Richard Nicholas

UCL Institute of Neurology

Phone: 0208 383 0675

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place