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

Diana Ho,Lara A Ray,Erica N Grodin,Brandon Towns

doi:10.1186/s13063-020-04842-w

Abstract

BackgroundAlcohol 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.MethodsIndividuals 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.DiscussionThe 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 registrationClinicalTrials.gov NCT04249882. Registered on 31 January 2020.

Highlights

Background and rationale {6a} Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the United States [1, 2]
The development of treatments for alcoholism has been difficult with over 20 medications having been tested in humans yet only three were able to receive Federal Drug Administration (FDA) approval, the last of which was granted over a decade ago [8]
The current study aims to develop and validate a novel early efficacy paradigm to screen medications for AUD

Summary

Introduction

Background and rationale {6a} Alcohol use disorder (AUD) is a highly prevalent, chronic relapsing disorder with a high disease burden in the United States [1, 2]. The Federal Drug Administration (FDA) has approved of four medications for AUD: disulfiram (Antabuse®), oral naltrexone (ReVia®), extended-release injectable naltrexone (Vivitrol®), and acamprosate (Campral®) [5]. These currently approved pharmacotherapies are only modestly effective, so there is still a great need to develop more effective interventions [6]. Phase 2 trials incorporate human laboratory paradigms to assess relevant clinical constructs, such as craving and subjective responses to alcohol. These controlled paradigms often lack the ecological validity of clinical trials. 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

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