Abstract

Background Gamma-hydroxybutyric acid (GHB) use disorder (GUD) is well known for its severe withdrawal syndrome. Currently, tapering with pharmaceutical GHB is the preferred option to mitigate withdrawal. The gamma-aminobutyric acid (GABA)-B receptor agonist baclofen could improve GHB detoxification, due to its longer half-life than pharmaceutical GHB and specific GABA-B receptor activation. However, clinical data on baclofen’s effectiveness to manage GHB withdrawal is limited. We aim to explore potential benefits of baclofen as an add-on to pharmaceutical GHB tapering in patients with GUD.

Methods This prospective, non-randomized, clinical trial consists of two phases: 1) a proof-of-concept phase (n=10) and 2) a dose-finding phase (n= 18). Primary objective of the proof-of-concept phase is to assess whether baclofen add-on therapy reduces the need for pharmaceutical GHB during inpatient detoxification. Safety and feasibility will also be assessed. Aim of the dose-finding phase is to explore the optimal baclofen dosage when used as add-on therapy during inpatient GHB detoxification. Criteria to start the second phase are that baclofen add-on therapy leads to a dose reduction of pharmaceutical GHB without severe side effects. GHB withdrawal symptoms and baclofen side effects will be monitored during GHB detoxification, using questionnaires.

Discussion We expect that baclofen add-on therapy will reduce the need for pharmaceutical GHB during inpatient GHB detoxification. This will likely result in a less intensive detoxification process for patients and will improve the overall feasibility of GHB detoxification. If the outcome of the current phase II trial is positive, either a replication phase II trial with a randomized blinded design or a lager phase III trial, would be a logical follow-up study to confirm the safety, feasibility and efficacy of baclofen add-on therapy during inpatient GHB detoxification.

Trial registration This study protocol is approved by the Medical Ethical Research Committee Oost-Nederland and Central Committee on Research Involving Human Subjects. The study is registered in the Clinical Trial Information System under EU CT-number: 2023-506167-34-02.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

EU CT-number: 2023-506167-34-02

Funding Statement

This study was not supported by any sponsor or funder.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study protocol is approved by the Medical Ethical Research Committee Oost-Nederland and Central Committee on Research Involving Human Subjects. The study is registered in the Clinical Trial Information System under EU CT-number: 2023-506167-34-02.

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Data availability statements

The datasets generated, used and/or analyzed during current study are available from the corresponding author upon reasonable request.

List of abbreviationsBZDbenzodiazepineGABAgamma-aminobutyric acidGHBgamma-hydroxybutyric acidGUDGHB use disorderMATEmeasurement of addicts for triage and evaluationOWSobjective withdrawal scaleSUDsubstance use disorderSWSsubjective withdrawal scaleTAUtreatment as usualVASVisual Analogue Scale