Evidence map›Paper›PMID 25409596›Full record

Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015

The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study.

Laura E Kwako, Primavera A Spagnolo, Melanie L Schwandt, Annika Thorsell, David T George, Reza Momenan, Daniel E Rio, Marilyn Huestis, Sebastien Anizan, Marta Concheiro and 2 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 2 pooled it
5.0field-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.

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

110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Effect of the CRFPsychopharmacology · 2016
    Trial
  8. The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016
    Trial
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

50 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

12 authors at 3 institutions in 1 country.

Laura E KwakoLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Primavera A SpagnoloLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Melanie L SchwandtLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Annika Thorsell1] Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA [2] Department of Clinical and Experimental Medicine, Linköping Univ., Linköping, Sweden.
David T GeorgeLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Reza MomenanLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Daniel E RioLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
Marilyn HuestisChemistry and Drug Metabolism Section, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
Sebastien AnizanChemistry and Drug Metabolism Section, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
Marta ConcheiroChemistry and Drug Metabolism Section, National Institute on Drug Abuse, NIH, Baltimore, MD, USA.
Rajita SinhaThe Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Markus HeiligLaboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
National Institute on Alcohol Abuse and Alcoholism · USNational Institute on Drug Abuse · USYale University · US

Funding

Yale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8M
fMRI Study of Motivation, Decision-Making, Reward, Risk, Aversion, Craving, impulsivity, and Stress in Alcohol Use DisordersZIAAA000124 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI MOMENAN, REZA · 2015 to 2025
$9.9M
Pharmacokinetics And Pharmacodynamics Of Drugs Of AbuseZIADA000414 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI SCHEIDWEILER, KARL · 2009 to 2016
$2.8M
Effect of Prazosin on Alcohol Craving, Stress Dysregulation and Alcohol RelapseR01AA020504 · NIAAA · YALE UNIVERSITY · PI FOX, HELEN CECILIA, SINHA, RAJITA · 2012 to 2016
$2.7M
6 · The paper itself

Abstract

Extensive preclinical data implicate corticotropin-releasing hormone (CRH), acting through its CRH1 receptor, in stress- and dependence-induced alcohol seeking. We evaluated pexacerfont, an orally available, brain penetrant CRH1 antagonist for its ability to suppress stress-induced alcohol craving and brain responses in treatment seeking alcohol-dependent patients in early abstinence. Fifty-four anxious alcohol-dependent participants were admitted to an inpatient unit at the NIH Clinical Center, completed withdrawal treatment, and were enrolled in a double-blind, randomized, placebo-controlled study with pexacerfont (300 mg/day for 7 days, followed by 100 mg/day for 23 days). After reaching steady state, participants were assessed for alcohol craving in response to stressful or alcohol-related cues, neuroendocrine responses to these stimuli, and functional magnetic resonance imaging (fMRI) responses to alcohol-related stimuli or stimuli with positive or negative emotional valence. A separate group of 10 patients received open-label pexacerfont following the same dosing regimen and had cerebrospinal fluid sampled to estimate central nervous system exposure. Pexacerfont treatment had no effect on alcohol craving, emotional responses, or anxiety. There was no effect of pexacerfont on neural responses to alcohol-related or affective stimuli. These results were obtained despite drug levels in cerebrospinal fluid (CSF) that predict close to 90% central CRH1 receptor occupancy. CRH1 antagonists have been grouped based on their receptor dissociation kinetics, with pexacerfont falling in a category characterized by fast dissociation. Our results may indicate that antagonists with slow offset are required for therapeutic efficacy. Alternatively, the extensive preclinical data on CRH1 antagonism as a mechanism to suppress alcohol seeking may not translate to humans.

Indexed as

AdultAgedAlcohol DeterrentsAlcoholismBrainCentral Nervous System DepressantsCravingCRF Receptor, Type 1CuesDouble-Blind MethodEmotionsEthanolFemaleHumansMagnetic Resonance ImagingMaleAlcohol DeterrentsCentral Nervous System DepressantsCRF Receptor, Type 1EthanolpexacerfontPyrazolesReceptors, Corticotropin-Releasing HormoneTriazines

Identifiers

PMID25409596
PMCPMC4367465
OpenAlexW2126747069

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.