Evidence map›Paper›PMID 29154277›Full record

Trial reportJournal of Alzheimer's disease : JAD2018

Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.

Gordon K Wilcock, Serge Gauthier, Giovanni B Frisoni, Jianping Jia, Jiri H Hardlund, Hans J Moebius, Peter Bentham, Karin A Kook, Bjoern O Schelter, Damon J Wischik and 12 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of Alzheimer's disease : JAD, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

114 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  6. Cross-disease protein aggregate interactions in neurodegeneration: from molecular mechanisms to therapeutic strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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54 more citing papers are in PubMed but not listed here.

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

22 authors.

Gordon K WilcockNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Serge GauthierMcGill Centre for Studies in Aging, Alzheimer's Disease Research Unit, and Douglas Mental Health University Institute, Montreal, QC, Canada.
Giovanni B FrisoniUniversity Hospitals and University of Geneva, Geneva, Switzerland.
Jianping JiaBeijing Institute for Brain Disorders Alzheimer's Disease Centre, Beijing, China.
Jiri H HardlundTauRx Therapeutics, Aberdeen, UK.
Hans J MoebiusMoebius-Consult, Baar, Switzerland.
Peter BenthamBirmingham and Solihull Mental Health Foundation Trust, Birmingham, UK.
Karin A KookSalamandra LLC, Bethesda, MD, USA.
Bjoern O SchelterInstitute for Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen, UK.
Damon J WischikComputer Laboratory, University of Cambridge, Cambridge, UK.
Charles S DavisCSD Biostatistics, Tucson, AZ, USA.
Roger T StaffAberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Vesna VuksanovicAberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Trevor AhearnAberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
Luc BracoudBioClinica, Lyon, France.
Kohkan ShamsiRadMD, New York, NY, USA.
Ken MarekMNI Imaging, New Haven, CT, USA.
John SeibylMNI Imaging, New Haven, CT, USA.
Gernot RiedelSchool of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
John M D StoreyTauRx Therapeutics, Aberdeen, UK.
Charles R HarringtonTauRx Therapeutics, Aberdeen, UK.
Claude M WischikTauRx Therapeutics, Aberdeen, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLMTM is being developed as a treatment for AD based on inhibition of tau aggregation.

objectivesTo examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD.

methodsMild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error.

resultsThe revised analyses were statistically significant at the required threshold of p < 0.025 in both comparisons for change in ADAS-cog, ADCS-ADL, MRI atrophy, and glucose uptake. The brain atrophy rate was initially typical of mild AD in both add-on and monotherapy groups, but after 9 months of treatment, the rate in monotherapy patients declined significantly to that reported for normal elderly controls. Differences in severity or diagnosis at baseline between monotherapy and add-on patients did not account for significant differences in favor of monotherapy.

conclusionsThe results are consistent with earlier studies in supporting the hypothesis that LMTM might be effective as monotherapy and that 4 mg twice a day may serve as well as higher doses. A further suitably randomized trial is required to test this hypothesis.

Indexed as

Treatment OutcomeAgedAged, 80 and overAlzheimer DiseaseAntipsychotic AgentsCohort StudiesDouble-Blind MethodFemaleHumansInternational CooperationMaleMental Status and Dementia TestsMethylene BlueMiddle AgedAntipsychotic AgentshydromethylthionineMethylene BlueADAS-cogAlzheimer’s diseaseamyloid proteinclinical trialcohort studymethylthioniniumtau proteintreatment

Identifiers

PMID29154277
PMCPMC5734125

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Registered trials

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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.