Evidence map›Paper›PMID 25223731›Full record

Trial reportBritish journal of clinical pharmacology2015

An exploratory double-blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease.

Sigurd D Süssmuth, Salman Haider, G Bernhard Landwehrmeyer, Ruth Farmer, Chris Frost, Giovanna Tripepi, Claus A Andersen, Marco Di Bacco, Claudia Lamanna, Enrica Diodato and 19 more

Abstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Sirtuin 1 Is Required for Optimal Mammarenavirus Multiplication.bioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.Molecular and cellular biochemistry · 2025
    Review
  10. Review
  11. Review
  12. Review
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  15. Review
  16. Review
  17. Article
  18. Role of epigenetics in corneal health and disease.Progress in retinal and eye research · 2025
    Review
  19. Article
  20. Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024
    Review

30 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

29 authors.

Sigurd D SüssmuthDepartment of Neurology, Ulm University Hospital, Ulm, Germany.
Salman Haider
G Bernhard Landwehrmeyer
Ruth Farmer
Chris Frost
Giovanna Tripepi
Claus A Andersen
Marco Di Bacco
Claudia Lamanna
Enrica Diodato
Luisa Massai
Daniela Diamanti
Elisa Mori
Letizia Magnoni
Jens Dreyhaupt
Karin Schiefele
David Craufurd
Carsten Saft
Monika Rudzinska
Danuta Ryglewicz
Michael Orth
Sebastian Brzozy
Anna Baran
Giuseppe Pollio
Ralph Andre
Sarah J Tabrizi
Borje Darpo
Goran Westerberg
PADDINGTON Consortium

Funding

Medical Research Council MR/L02053X/1
6 · The paper itself

Abstract

aimsSelisistat, a selective SirT1 inhibitor is being developed as a potentially disease-modifying therapeutic for Huntington's disease (HD). This was the first study of selisistat in HD patients and was primarily aimed at development of pharmacodynamic biomarkers.

methodsThis was a randomized, double-blind, placebo-controlled, multicentre exploratory study. Fifty-five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.

resultsSelisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady-state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.

conclusionsSelisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.

Indexed as

Administration, OralAdolescentAdultAgedArea Under CurveCarbazolesCognitionDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleFemaleHumansHuntington DiseaseMaleMiddle AgedNeuropsychological Tests6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamideCarbazolesSIRT1 protein, humanSirtuin 1Huntington's diseasepharmacodynamicspharmacokineticsselisistatSirT1 inhibition

Identifiers

PMID25223731
PMCPMC4345957

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.