Evidence mapPaperPMID 41474196Full record

Trial reportThe international journal of neuropsychopharmacology2026

Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder.

Ryan E Tyler, Rabea K Pfaff, Raja Muhammad Naseer Khan, Anna Loften, Ryan Zurick, Yi Zeng, Oluwatobi T Arisa, Charlotte Harvey, Fatemeh Akhlaghi, William D Figg and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The international journal of neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02707055 (A Novel Compound for Alcoholism Treatment), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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.

NCT02707055 phase2terminatednot on this map

A Novel Compound for Alcoholism Treatment: A Translational Strategy - Part II

TypeinterventionalSponsorNational Institute on Alcohol Abuse and Alcoholism (NIAAA)Ran2016 to 2020Enrolled42ConditionsAlcoholismArmsPF-05190457, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Ryan E TylerClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.
Rabea K PfaffClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.
Raja Muhammad Naseer KhanClinical Pharmacology Laboratory, Clinical Center, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0001-6875-1669
Anna LoftenClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.
Ryan ZurickTranslational Analytical Core, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD, United States.
Yi ZengClinical Pharmacology Laboratory, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
Oluwatobi T ArisaClinical Pharmacology Laboratory, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
Charlotte HarveyClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.
Fatemeh AkhlaghiVentyx Biosciences, San Diego, CA, United States.
William D FiggClinical Pharmacology Laboratory, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
Mehdi FarokhniaClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.ORCID 0000-0003-0902-4212
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, MD, United States.ORCID 0000-0002-4495-037X

Funding

Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)ZIADA000635 · NATIONAL INSTITUTE ON DRUG ABUSE · 2025 to 2025
$2.7M
Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section ZIA-DA000635Intramural NIH HHS ZIA DA000635NCATS NIH HHS UH2 TR000963NCATS NIH HHS UH3 TR000963NIAAA Division of Intramural Clinical and Biological Research (DICBR)NIDA Intramural Research Program (IRP)NIDA IRP Translational Analytical Core (TAC)NIGMS NIH HHS 1FI2GM154714-01NIGMS NIH HHS FI2 GM154714NIH Center on Compulsive Behavior Fellowship UH2/UH3-TR000963Swedish Medical Society SLS-998225
6 · The paper itself

Abstract

objectiveGhrelin and liver-expressed antimicrobial peptide 2 (LEAP2) act via the growth hormone secretagogue receptor (GHSR), which modulates feeding, alcohol use, and endocrine and immune system function. The GHSR blocker PF-5190457 has potential as a novel pharmacotherapy for alcohol use disorder (AUD). This study aimed to characterize the effects of PF-5190457 on endocrine and immune markers in individuals with AUD.

methodsPre-planned analyses used data from a randomized, double-blind, placebo-controlled, crossover human laboratory study in recently abstinent inpatients with AUD (N = 29; 8 females). Participants received PF-5190457 (100 mg twice daily) or matched placebo for 5+ days, separated by 2+ washout days. Blood was collected daily prior to dosing (T1). On days 4+, behavioral testing occurred post-dosing, followed by an additional blood collection ~2 hours post dosing (T2). Pharmacokinetic (PK: PF-5190457 and its active metabolite PF-6870961) and pharmacodynamic (PD: comprehensive panel of endocrine and immune markers) parameters were assessed over the course of dosing days. Additional exploratory analyses examined relationships between PK, PD, and behavioral measures.

resultsPF-5190457 and PF-6870961 concentrations peaked at T2 and were elevated at T1 under drug vs placebo. LEAP2 levels were reduced under drug vs placebo but rebounded on the first washout day. PF-5190457 dramatically reduced growth hormone (GH) at T2, followed by an elevation of GH at T1 the following day. No other endocrine or immune markers differed significantly between drug and placebo. GH at T1 negatively correlated with the number of calories selected during a cafeteria-like virtual reality buffet experiment under drug, but not placebo conditions.

conclusionsGHSR blockade with repeated dosing of PF-5190457 changed LEAP2 and GH concentrations but produced overall negligible effects on the endocrine and immune systems. These results further characterize the ghrelin system in AUD and its potential as a therapeutic target.

trial registrationClinicalTrials.gov Identifier: NCT02707055; registered November 3, 2016.

Indexed as

Alcohol AbstinenceAlcoholismReceptors, GhrelinAdultAntimicrobial Cationic PeptidesAzetidinesBlood ProteinsCross-Over StudiesDouble-Blind MethodFemaleGhrelinHumansMaleMiddle AgedSpiro CompoundsYoung AdultAntimicrobial Cationic PeptidesAzetidinesBlood ProteinsGhrelinliver-expressed antimicrobial peptide 2, humanPF-5190457Receptors, GhrelinSpiro CompoundsalcoholghrelinGHSRgrowth hormoneLEAP2PF-6870961

Identifiers

PMID41474196
PMCPMC12866918

What Socratic holds

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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 Socratic graph.