Evidence map›Paper›PMID 39691073›Full record

Trial reportEuropean journal of neurology2025

Vascular risk factors are associated with grey matter atrophy in secondary progressive multiple sclerosis.

Nevin A John, Yingtong Li, Floriana De Angelis, Jonathan Stutters, Ferran Prados, Anisha Doshi, Alberto Calvi, Thomas Williams, Domenico Plantone, Thanh Phan and 4 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01910259 (A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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.

NCT01910259 phase2completednot on this map

A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.

TypeinterventionalSponsorUniversity College, LondonRan2014 to 2018Enrolled445ConditionsSecondary Progressive Multiple SclerosisArmsAmiloride, Riluzole, Fluoxetine, Placebo
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Trial
  3. Article
  4. Article
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

14 authors.

Nevin A JohnDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Yingtong LiDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Floriana De AngelisQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Jonathan StuttersQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.ORCID https://orcid.org/0000-0002-9151-0844
Ferran PradosQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Anisha DoshiQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Alberto CalviLaboratory of Advanced Imaging in Neuroimmunological Diseases (imaginEM), Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain.ORCID https://orcid.org/0000-0002-1953-2803
Thomas WilliamsQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.ORCID https://orcid.org/0000-0002-8197-0177
Domenico PlantoneDepartment of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy.
Thanh PhanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Claudia A M Gandini Wheeler-KingshottQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Frederik BarkhofQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Jeremy ChatawayQueen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
MS‐SMART Investigators

Funding

NIHR EME 11/30/11
6 · The paper itself

Abstract

backgroundComorbidities including vascular risk factors can be associated with whole and regional brain atrophy in multiple sclerosis (MS). This has been examined in mixed MS cohorts in prospective or observational studies; however, the association between vascular comorbidities (VCM) in secondary progressive MS (SPMS) and brain atrophy has been less well studied. The aim was to investigate the cross-sectional and longitudinal association between VCM, comorbidity burden and brain atrophy in SPMS.

methodsPost hoc analysis of 445 participants from the MS-Secondary Progressive multi-arm trial (MS-SMART)-a multi-arm multicentre phase-2b randomised placebo-controlled trial of three agents in SPMS (NCT01910259). VCM (hypertension, hyperlipidaemia) but also asthma, hypothyroidism and osteoporosis were recorded. Regional and whole brain volume (WBV), and percentage brain volume change were calculated using SIENAX and SIENA, respectively. Multiple linear regression was used to investigate the cross-sectional and longitudinal relationships between VCM, overall comorbidity count and whole brain, grey matter (GM) and white matter (WM) atrophy.

resultsThe cohort was predominantly female (67%), mean age 55 with median EDSS 6.0. In total, 13% and 9% had hypertension and hyperlipidaemia, respectively. In cross-sectional regression models, VCM was associated with decreased cortical GM volume [(hypertension β = -0.30, 95%CI -0.54 to -0.06, p = 0.01) (hyperlipidaemia β = -0.37, 95%CI -0.64 to -0.09, p = 0.008)]; but not WBV. Having ≥2 comorbidities was also associated with decreased cortical GM volume (β = -0.36, 95%CI -0.61 to -0.10, p = 0.007). No relationship was observed between VCM/comorbidity count and whole brain or GM atrophy rate over 96 weeks.

conclusionsPeople with SPMS with VCM or increased overall comorbidity burden showed reduced whole brain and especially cortical grey matter volumes, but no significant impact on subsequent 2-year atrophy rate was detected.

Indexed as

AtrophyGray MatterMultiple Sclerosis, Chronic ProgressiveAdultAgedComorbidityCross-Sectional StudiesFemaleHumansHypertensionLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedRisk FactorsWhite Mattercomorbiditiesmultiple sclerosissecondary progressive

Identifiers

PMID39691073
PMCPMC11653023

What OpenQuestion holds

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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.