Evidence map›Paper›PMID 24650045›Full record

ArticleJournal of pineal research2014

Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis.

Helen F Galley, Damon A Lowes, Lee Allen, Gary Cameron, Lorna S Aucott, Nigel R Webster

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of pineal research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03764020 (A Triple Blinded Randomized Controlled Trial of Oral Melatonin in Elevated Blood Pressure Individual), which is not on this map. Cited by 86 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 5 pooled it
5.6field-weighted citation impact, top 3% 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.

NCT03764020 phase3unknown statusnot on this mapstarted 2019, after this paper: background citation

A Triple Blinded Randomized Controlled Trial of Oral Melatonin in Elevated Blood Pressure Individual (MRCTEBP)

TypeinterventionalSponsorTehran University of Medical SciencesRan2019 to 2019Enrolled320ConditionsElevated Blood PressureArmsPlacebo oral capsule/placebo comparator, Melatonin/experimental
3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 5 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. The oxidative stress paradigm in arbovirus infections: mechanisms and therapeutic insights.Redox report : communications in free radical research · 2026
    Review
  19. Review
  20. Review

26 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

6 authors at 2 institutions in 1 country.

Helen F GalleyDivision of Applied Health, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK; Intensive Care Unit, Aberdeen Royal Infirmary, Aberdeen, UK.
Damon A Lowes
Lee Allen
Gary Cameron
Lorna S Aucott
Nigel R Webster
University of Aberdeen · GBAberdeen Royal Infirmary · GB

Funding

Chief Scientist Office ETM/167
6 · The paper itself

Abstract

Sepsis is a massive inflammatory response mediated by infection, characterized by oxidative stress, release of cytokines, and mitochondrial dysfunction. Melatonin accumulates in mitochondria, and both it and its metabolites have potent antioxidant and anti-inflammatory activities and may be useful in sepsis. We undertook a phase I dose escalation study in healthy volunteers to assess the tolerability and pharmacokinetics of 20, 30, 50, and 100 mg oral doses of melatonin. In addition, we developed an ex vivo whole blood model under conditions mimicking sepsis to determine the bioactivity of melatonin and the major metabolite 6-hydroxymelatonin at relevant concentrations. For the phase I trial, oral melatonin was given to five subjects in each dose cohort (n = 20). Blood and urine were collected for measurement of melatonin and 6-hydroxymelatonin, and symptoms and physiological measures were assessed. Validated sleep scales were completed. No adverse effects after oral melatonin, other than mild transient drowsiness with no effects on sleeping patterns, were seen, and no symptoms were reported. Melatonin was rapidly cleared at all doses with a median [range] elimination half-life of 51.7 [29.5-63.2] min across all doses. There was considerable variability in maximum melatonin levels within each dose cohort, but 6-hydoxymelatonin sulfate levels were less variable and remained stable for several hours. For the ex vivo study, blood from 20 volunteers was treated with lipopolysaccharide and peptidoglycan plus a range of concentrations of melatonin/6-hydroxymelatonin. Both melatonin and 6-hydroxymelatonin had beneficial effects on sepsis-induced mitochondrial dysfunction, oxidative stress, and cytokine responses at concentrations similar to those achieved in vivo.

Indexed as

AntioxidantsMelatoninAdultCytokinesDose-Response Relationship, DrugHumansMaleOxidative StressSepsisAntioxidantsCytokinesMelatonin6-hydroxymelatonincytokinesmelatoninphase I clinical trialsepsis

Identifiers

PMID24650045
PMCPMC4279949
OpenAlexW2097588095

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.