Evidence map›Paper›PMID 34225765›Full record

ArticleTrials2021

SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia-a phase II randomised control trial study protocol.

Caroline McCarthy, Joseph Sacco, Stefano Fedele, Michael Ho, Stephen Porter, Triantafillos Liloglou, Bill Greenhalf, Max Robinson, Bridget Young, Silvia Cicconi and 5 more

Open access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.1field-weighted citation impact, top 8% 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.

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

8 citing papers in PubMed, 12 citations in OpenAlex.

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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

15 authors at 5 institutions in 1 country.

Caroline McCarthyDepartment of Oral Medicine, Liverpool University Dental Hospital, Pembroke Place, Liverpool, L3 5PS, UK. carolmc2@liverpool.ac.uk.ORCID http://orcid.org/0000-0003-3979-6643
Joseph SaccoInstitute of Systems, Molecular and Integrative Biology, The University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Stefano FedeleUniversity College London, UCL Eastman Dental Institute and NIHR UCLH Biomedical Research Centre, 21 University Street, London, WC1E 6DE, UK.
Michael HoLeeds Teaching Hospitals NHS Trust, Oral and Maxillofacial Surgery, Leeds Dental Institute, Clarendon Way, Leeds, LS2 9LU, UK.
Stephen PorterUniversity College London, UCL Eastman Dental Institute, 21 University Street, London, WC1E 6DE, UK.
Triantafillos LiloglouInstitute of Systems, Molecular and Integrative Biology, The University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Bill GreenhalfGCP Laboratory Facility, Molecular and Clinical Cancer Medicine, University of Liverpool, 3rd Floor UCD Block, Duncan Building, Daulby Street, Liverpool, L69 3GA, UK.
Max RobinsonDept of Cellular Pathology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.
Bridget YoungDepartment of Psychological Sciences, Institute of Psychology, Health and Society, University of Liverpool, Whelan Building, Brownlow Hill, Liverpool, L69 3GB, UK.
Silvia CicconiLiverpool Clinical Trials Centre, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK.
Seema ChauhanLiverpool Health Partners SPARK, 1st Floor IC3, Liverpool Science Park, 131 Mount Pleasant, Liverpool, L3 5TF, UK.
Binyam TesfayeLiverpool Clinical Trials Centre, University of Liverpool, 1st Floor, Mersey Bio, Liverpool, L69 7ZB, UK.
Richard JacksonLiverpool Clinical Trials Centre, Block C, Waterhouse Building, 1-3 Brownlow Street, Liverpool, L69 3GL, UK.
Frances SherrattDepartment of Public Health, Policy and Systems, University of Liverpool, B209, 2nd Floor Block B, Waterhouse Building, 1-5 Dover Street, Liverpool, L3 5DA, UK.
Richard ShawLiverpool Head and Neck Centre; Institute of Systems, Molecular and Integrative Biology, The University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK.
University of Liverpool · GBEastman Dental Hospital · GBLeeds Teaching Hospitals NHS Trust · GBRoyal Victoria Infirmary · GBUCL Biomedical Research Centre · GB

Funding

Efficacy and Mechanism Evaluation Programme (GB) 14/209/13Medical Research Council MR/N005872/1
6 · The paper itself

Abstract

backgroundSodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study.

methodsOne hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. DISCUSSION: The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial.

trial registrationThe trial is registered with the European Clinical Trials Database ( Eudra-CT 2018-000197-30 ). ( http://www.isrctn.com/ISRCTN12448611 ). The trial was prospectively registered on 24/04/2018.

Indexed as

COVID-19Valproic AcidClinical Trials, Phase II as TopicEpigenesis, GeneticFemaleHumansRandomized Controlled Trials as TopicSARS-CoV-2Treatment OutcomeValproic AcidChemopreventionDrug repurposingEpigenetic reprogrammingOral epithelial dysplasiaRandomised controlled trialSodium valproate

Identifiers

PMID34225765
PMCPMC8256209
OpenAlexW3181606822

What OpenQuestion holds

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Registered trials

None linked

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.