Evidence map›Paper›PMID 35031587›Full record

Trial reportNeurology(R) neuroimmunology & neuroinflammation2022

Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial.

Thomas E Williams, Katherine P Holdsworth, Jennifer M Nicholas, Arman Eshaghi, Theodora Katsanouli, Henrietta Wellington, Amanda Heslegrave, Henrik Zetterberg, Chris Frost, Jeremy Chataway

2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology(R) neuroimmunology & neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00647348 phase2completednot on this map

A Phase II Randomised, Placebo-controlled Clinical Trial of Simvastatin in Patients With Secondary Progressive Multiple Sclerosis.

TypeinterventionalSponsorImperial College LondonRan2008 to 2011Enrolled140ConditionsSecondary Progressive Multiple SclerosisArmsSimvastatin, Placebo
NCT03387670 phase3completednot on this map

A Phase 3 Randomised, Double Blind, Clinical Trial Investigating the Effectiveness of Repurposed Simvastatin Compared to Placebo, in Secondary Progressive Multiple Sclerosis, in Slowing the Progression of Disability

TypeinterventionalSponsorUniversity College, LondonRan2018 to 2024Enrolled964ConditionsSecondary Progressive Multiple Sclerosis (SPMS)ArmsSimvastatin, Placebo
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. The Role of Lipid Alteration in Multiple Sclerosis.International journal of molecular sciences · 2026
    Review
  6. Review
  7. Neurofilament heavy chain in secondary progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Thomas E WilliamsFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom. thomas.e.williams@ucl.ac.uk.ORCID 0000-0002-8197-0177
Katherine P HoldsworthFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Jennifer M NicholasFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Arman EshaghiFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.ORCID 0000-0002-6652-3512
Theodora KatsanouliFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Henrietta WellingtonFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Amanda HeslegraveFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Henrik ZetterbergFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Chris FrostFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
Jeremy ChatawayFrom the Queen Square Multiple Sclerosis Centre (T.E.W., A.E., J.C.), Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London; National Hospital of Neurology and Neurosurgery (T.E.W., J.C.), London; London School of Hygiene and Tropical Medicine (K.P.H., J.M.N., T.K., C.F.); and UK Dementia Research Institute at UCL (H.W., A.H., H.Z.), United Kingdom.
National Hospital for Neurology and Neurosurgery · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesImproved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS.

methodsThe MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity.

resultsA total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; DISCUSSION: We found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS. TRIAL REGISTRATION INFORMATION: MS-STAT: NCT00647348. CLASSIFICATION OF EVIDENCE: This study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS.

Indexed as

Multiple Sclerosis, Chronic ProgressiveAdultBiomarkersFemaleHumansMaleMiddle AgedNeurofilament ProteinsNeuroprotective AgentsOutcome Assessment, Health CareSimvastatinBiomarkersneurofilament protein LNeurofilament ProteinsNeuroprotective AgentsSimvastatin

Identifiers

PMID35031587
PMCPMC8759719
OpenAlexW4206744034

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.