METHODS AND ANALYSIS: Initially, during Phase I of the study, the serum level of IL-1β, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1β, IL-6 and TNF-α; changes in ERP and fecal microbiota content.
TRIAL REGISTRATION NUMBER: NCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023.
METHODS: Initially, after 2 weeks of in-patient detoxification, 120 patients with alcohol use disorder will be randomized into three groups (VRET, ACT, and TAU control groups) via stratified permuted block randomization in a 1:1:1 ratio. Baseline assessment (t0) commences, whereby all the participants will be administered with sociodemographic, clinical, and alcohol use characteristics questionnaire, such as Alcohol Use Disorder Identification Test (AUDIT), Penn Alcohol Craving Scale (PACS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), while event-related potential (ERP) detection in electroencephalogram (EEG) will also be carried out. Then, 4 weeks of VRET, ACT, and non-therapeutic supportive activities will be conducted in the three respective groups. For the subsequent three assessment timelines (t1, t2, and t3), the alcohol use characteristic questionnaire, such as AUDIT, PACS, HAM-D, HAM-A, and ERP monitoring, will be re-administered to all participants.
DISCUSSION: As data on the effects of non-pharmacological interventions, such as VRET and ACT, on the treatment of alcohol craving and preventing relapse in alcohol use disorder are lacking, this RCT fills the research gap by providing these important data to treating clinicians. If proven efficacious, the efficacy of VRET and ACT for the treatment of other substance use disorders should also be investigated in future.
CLINICAL TRIAL REGISTRATION: NCT05841823 (ClinicalTrials.gov).
METHODS AND ANALYSIS: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.
ETHICS AND DISSEMINATION: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03782792; Pre-results.