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A novel human laboratory model for screening medications for alcohol use disorder

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high pr...

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Autores principales: Ho, Diana, Towns, Brandon, Grodin, Erica N., Ray, Lara A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681966/
https://www.ncbi.nlm.nih.gov/pubmed/33225963
http://dx.doi.org/10.1186/s13063-020-04842-w
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author Ho, Diana
Towns, Brandon
Grodin, Erica N.
Ray, Lara A.
author_facet Ho, Diana
Towns, Brandon
Grodin, Erica N.
Ray, Lara A.
author_sort Ho, Diana
collection PubMed
description BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline. METHODS: Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions. DISCUSSION: The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04249882. Registered on 31 January 2020.
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spelling pubmed-76819662020-11-23 A novel human laboratory model for screening medications for alcohol use disorder Ho, Diana Towns, Brandon Grodin, Erica N. Ray, Lara A. Trials Study Protocol BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the USA. Pharmacotherapy is a promising treatment method for AUD; however, the few FDA-approved medications are only modestly effective. Medications development for AUD is a high priority research area, but the cumbersome drug development process hinders many potential compounds from reaching approval. One area with major opportunities for improvement is the process of screening novel compounds for initial efficacy, also known as early phase 2 trials. Early phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. However, these controlled paradigms often lack the ecological validity of clinical trials. Therefore, early phase 2 trials can be more efficient and clinically meaningful if they combine the internal validity of experimental laboratory testing with the external validity of clinical trials. To that end, the current study aims to develop and validate a novel early efficacy paradigm, informed by smoking cessation literature, to screen novel medications for AUD. As an established AUD medication, naltrexone will serve as an active control to test both the practice quit attempt model and the efficacy of a promising AUD pharmacotherapy, varenicline. METHODS: Individuals with current AUD reporting intrinsic motivation to change their drinking will complete a week-long “practice quit attempt” while on study medication. Participants are randomized and blinded to either naltrexone, varenicline, or placebo. During the practice quit attempt, participants will complete daily visits over the phone and fill out online questionnaires regarding their drinking, alcohol craving, and mood. Additionally, participants will undergo two alcohol cue-reactivity sessions. DISCUSSION: The successful completion of this study will advance medications development by proposing and validating a novel early efficacy model for screening AUD pharmacotherapies, which in turn can serve as an efficient strategy for making go/no-go decisions as to whether to proceed with clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04249882. Registered on 31 January 2020. BioMed Central 2020-11-23 /pmc/articles/PMC7681966/ /pubmed/33225963 http://dx.doi.org/10.1186/s13063-020-04842-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Ho, Diana
Towns, Brandon
Grodin, Erica N.
Ray, Lara A.
A novel human laboratory model for screening medications for alcohol use disorder
title A novel human laboratory model for screening medications for alcohol use disorder
title_full A novel human laboratory model for screening medications for alcohol use disorder
title_fullStr A novel human laboratory model for screening medications for alcohol use disorder
title_full_unstemmed A novel human laboratory model for screening medications for alcohol use disorder
title_short A novel human laboratory model for screening medications for alcohol use disorder
title_sort novel human laboratory model for screening medications for alcohol use disorder
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681966/
https://www.ncbi.nlm.nih.gov/pubmed/33225963
http://dx.doi.org/10.1186/s13063-020-04842-w
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