Evidence map›Paper›PMID 27371157›Full record

Trial reportProgress in neuro-psychopharmacology & biological psychiatry2016

Task-related fMRI responses to a nicotinic acetylcholine receptor partial agonist in schizophrenia: A randomized trial.

Deanna M Barch, Stephen R Marder, Michael P Harms, L Fredrik Jarskog, Robert W Buchanan, Will Cronenwett, Li-Shiun Chen, Markus Weiss, Ralph P Maguire, Nicole Pezous and 5 more

2 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Progress in neuro-psychopharmacology & biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 24% 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.

NCT00825539 phase1 / phase2completednot on this map

A Single-dose, Placebo-controlled, Stratified, Randomized, Double-blind, Crossover to Study Pharmacodynamic Effects of AQW051 Followed by a 4-week Multiple-dose Safety and Tolerability in People With Chronic Stable Schizophrenia.

TypeinterventionalSponsorNovartis PharmaceuticalsRan2009 to 2011Enrolled68ConditionsSchizophreniaArmsAQW051, Placebo
NCT05282277 phase4recruitingnot on this mapstarted 2022, after this paper: background citation

Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

TypeinterventionalSponsorUniversity of North Carolina, Chapel HillRan2022 to 2026Enrolled103ConditionsDepression, Psychosis, AnhedoniaArmsTransdermal Estradiol, Micronized Progesterone, Matching Placebo Patch, Raclopride C11
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019
    Review
  5. Article
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 6 institutions in 3 countries.

Deanna M BarchDepartment of Psychology, Washington University, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: dbarch@wustl.edu.
Stephen R MarderSemel Institute for Neuroscience at UCLA, Los Angeles, CA, USA; VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, USA. Electronic address: SMarder@mednet.ucla.edu.
Michael P HarmsDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: mharms@wustl.edu.
L Fredrik JarskogDepartment of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: lars_jarskog@med.unc.edu.
Robert W BuchananMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: rwbuchanan@mprc.umaryland.edu.
Will CronenwettDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: w-cronenwett@northwestern.edu.
Li-Shiun ChenDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: chenli@psychiatry.wustl.edu.
Markus WeissNovartis Pharma AG, Basel, Switzerland. Electronic address: markus.weiss@novartis.com.
Ralph P MaguireNovartis Pharma AG, Basel, Switzerland. Electronic address: paul.maguire@novartis.com.
Nicole PezousNovartis Pharma AG, Basel, Switzerland. Electronic address: nicole.pezous@novartis.com.
Dominik FeuerbachNovartis Pharma AG, Basel, Switzerland. Electronic address: dominik.feuerbach@novartis.com.
Cristina Lopez-LopezNovartis Pharma AG, Basel, Switzerland. Electronic address: cristina.lopez_lopez@novartis.com.
Donald R JohnsNovartis Pharma AG, Basel, Switzerland. Electronic address: donald.johns@biogen.com.
Rhett B BehrjeNovartis Pharma AG, Basel, Switzerland. Electronic address: rhett.behrje@novartis.com.
Baltazar Gomez-MancillaNovartis Pharma AG, Basel, Switzerland; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada. Electronic address: baltazar.gomezmancilla@novartis.com.
Novartis (Switzerland) · CHWashington University in St. Louis · USNorthwestern University · USUniversity of Maryland, Baltimore · USUniversity of North Carolina at Chapel Hill · USWest Los Angeles College · US

Funding

The Effects of Kynurenine Aminotransferase Inhibition in People with SchizophreniaP50MH103222 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI SCHWARCZ, ROBERT · 2014 to 2023
$25.2M
STRUCTURE, FUNCTION AND COGNITION IN SCHIZOPHRENIAP50MH071616 · NIMH · WASHINGTON UNIVERSITY · PI BARCH, DEANNA · 2004 to 2008
$11.2M
NIMH NIH HHS P50 MH071616NIMH NIH HHS P50 MH103222
6 · The paper itself

Abstract

introductionAQW051, an α7-nicotinic acetylcholine receptor partial agonist, enhanced cognitive function in rodent models of learning and memory. This study evaluated brain activation during performance of a working memory task (WMT) and an episodic memory task (EMT), and the effect of AQW051 on task-related brain activation and performance in subjects with schizophrenia.

methodsThis was a double-blind, randomized, placebo-controlled, multicenter, 2-period cross-over trial (NCT00825539) in participants with chronic, stable schizophrenia. Participants, stratified according to smoking status, were randomized (1:1:1:1:1:1) to 1 of 6 sequence groups that determined the study drug dose (AQW051 7.5mg, 50mg or 100mg) and order of administration versus placebo. The primary outcome was brain activation in a priori target regions of interest (ROIs) during performance of the WMT and EMT, measured using functional magnetic resonance imaging. The effect of AQW051 on task-related (EMT and WMT) brain activation and performance was also assessed, as were safety and tolerability.

resultsOverall, 60 of 68 enrolled participants completed the study (AQW051 then placebo: 7.5mg n=9; 50mg n=11; 100mg n=10. Placebo then AQW051: 7.5mg n=10; 50mg n=11; 100mg n=9). Significant task-related brain activation (5% significance level) was observed with placebo. During the WMT, a medium effect size was observed in the inferior prefrontal cortex with AQW051 100mg versus placebo (0.431; p=0.105). During the EMT encoding phase, a large effect size was observed in the anterior hippocampus (0.795; p=0.007) and a medium effect size in the posterior hippocampus (0.476; p=0.079) with AQW051 7.5mg. No other medium/large effect sizes were observed with any dose on either task. Effects on brain activation were generally not associated with changes in cognitive performance. AQW051 was well tolerated with an acceptable safety profile.

conclusionsOverall, no consistent effects of AQW051 on brain regions involved in the performance of a WMT or EMT were observed; however, this study presents a model for evaluating potential response to pharmacological interventions for cognitive impairment in schizophrenia.

Indexed as

Magnetic Resonance ImagingAdolescentAdultAzabicyclo CompoundsBrainCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansImage Processing, Computer-AssistedMaleMemory DisordersMemory, EpisodicMemory, Short-TermMiddle Aged3-(6-p-tolylpyridin-3-yloxy)-1-azabicyclo(2.2.2)octaneAzabicyclo CompoundsNicotinic AgonistsOxygenPyridinesReceptors, NicotinicAQW051Clinical trialFunctional magnetic resonance imagingNicotinic acetylcholine receptor (nAChR)Schizophrenia

Identifiers

PMID27371157
PMCPMC6432789
OpenAlexW2464082897

What OpenQuestion holds

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LicenceTDM
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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 OpenQuestion graph.