ArticlePloS one2013
Biomarker report from the phase II lamotrigine trial in secondary progressive MS - neurofilament as a surrogate of disease progression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02104661 (OxCarbazepine as a Neuroprotective Agent in MS), which is not on this map. Cited by 27 papers, 2 of them syntheses that pooled 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.
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.
OxCarbazepine as a Neuroprotective Agent in MS: A Phase 2a Trial
Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Neurofilaments in progressive multiple sclerosis: a systematic review.Journal of neurology · 2021Pooled it
- Neurofilaments as Biomarkers for Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.PloS one · 2016Pooled it
- Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial.Neurology(R) neuroimmunology & neuroinflammation · 2022Trial
- Serum neurofilament is associated with progression of brain atrophy and disability in early MS.Neurology · 2017Trial
- Neurofilaments: A Promising Diagnostic and Prognostic Biomarker in Multiple Sclerosis.Annals of neurosciences · 2026Review
- Neurofilament heavy chain in secondary progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2025Article
- Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis.Brain sciences · 2025Review
- Neuroprotection in an Experimental Model of Multiple Sclerosis via Opening of Big Conductance, Calcium-Activated Potassium Channels.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Intrathecal versus Peripheral Inflammatory Protein Profile in MS Patients at Diagnosis: A Comprehensive Investigation on Serum and CSF.International journal of molecular sciences · 2023Article
- Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review.Frontiers in molecular neuroscience · 2023Review
- A focus on secondary progressive multiple sclerosis (SPMS): challenges in diagnosis and definition.Journal of neurology · 2021Review
- Facing the urgency of therapies for progressive MS - a Progressive MS Alliance proposal.Nature reviews. Neurology · 2021Review
- Retinal Nerve Fiber Layer Thickness Correlates with Serum and Cerebrospinal Fluid Neurofilament Levels and is Associated with Current Disability in Multiple Sclerosis.Noro psikiyatri arsivi · 2021Article
- The Evolution of Neurofilament Light Chain in Multiple Sclerosis.Frontiers in neuroscience · 2021Review
- Oligodendrocytes, BK channels and the preservation of myelin.F1000Research · 2021Review
- ALS Yeast Models-Past Success Stories and New Opportunities.Frontiers in molecular neuroscience · 2018Review
- Neurofilament light chain as a biological marker for multiple sclerosis: a meta-analysis study.Neuropsychiatric disease and treatment · 2018Review
- Protease-activated receptor-1 activation by granzyme B causes neurotoxicity that is augmented by interleukin-1β.Journal of neuroinflammation · 2017Article
- The influence of sodium on pathophysiology of multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2017Review
- Experimental autoimmune encephalomyelitis from a tissue energy perspective.F1000Research · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLamotrigine trial in SPMS was a randomised control trial to assess whether partial blockade of sodium channels has a neuroprotective effect. The current study was an additional study to investigate the value of neurofilament (NfH) and other biomarkers in predicting prognosis and/or response to treatment.
methodsSPMS patients who attended the NHNN or the Royal Free Hospital, UK, eligible for inclusion were invited to participate in the biomarker study. Primary outcome was whether lamotrigine would significantly reduce detectable serum NfH at 0-12, 12-24 and 0-24 months compared to placebo. Other serum/plasma and CSF biomarkers were also explored.
resultsTreatment effect by comparing absolute changes in NfH between the lamotrigine and placebo group showed no difference, however based on serum lamotrigine adherence there was significant decline in NfH (NfH 12-24 months p=0.043, Nfh 0-24 months p=0.023). Serum NfH correlated with disability: walking times, 9-HPT (non-dominant hand), PASAT, z-score, MSIS-29 (psychological) and EDSS and MRI cerebral atrophy and MTR. Other biomarkers explored in this study were not found to be significantly associated, aside from that of plasma osteopontin.
conclusionsThe relations between NfH and clinical scores of disability and MRI measures of atrophy and disease burden support NfH being a potential surrogate endpoint complementing MRI in neuroprotective trials and sample sizes for such trials are presented here. We did not observe a reduction in NfH levels between the Lamotrigine and placebo arms, however, the reduction in serum NfH levels based on lamotrigine adherence points to a possible neuroprotective effect of lamotrigine on axonal degeneration.
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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.