European journal of internal medicine
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Eur. J. Intern. Med. · Sep 2024
Randomized Controlled Trial Multicenter StudyLow-dose ondansetron: A candidate prospective precision medicine to treat alcohol use disorder endophenotypes.
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects. ⋯ In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
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Eur. J. Intern. Med. · Sep 2024
Randomized Controlled TrialSafety and compliance of long-term low-dose ondansetron in alcohol use disorder treatment.
The increasing prevalence of alcohol use disorder (AUD) and the parallel surge in alcohol-associated liver disease (ALD) emphasize the urgent need for comprehensive alcohol management strategies. Low-dose ondansetron (AD04, a 5-HT3 antagonist) was shown recently to be a promising treatment for AUD with a specific genotypic profile (5-marker). The liver safety of AD04 has never been evaluated in subjects with AUD. The aim of the present study was to assess the liver safety profile of AD04 compared with placebo in subjects with AUD. ⋯ Low-dose AD04 has the potential to be a safe treatment option for subjects with AUD and ALD, indicating the need for an RCT for this specific cohort. Such a trial would pave the way for the design of a precision treatment for combined AUD with ALD.
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Eur. J. Intern. Med. · Sep 2024
Development and validation of a novel sleep health score in the sleep heart health study.
There is a lack of consensus in evaluating multidimensional sleep health, especially concerning its implication for mortality. A validated multidimensional sleep health score is the foundation of effective interventions. ⋯ This study constructed and validated a novel multidimensional sleep health score to better predict death based on sleep, with significant associations between sleep composite score and all-cause mortality. Integrating questionnaire information and sleep microstructures, our sleep composite score is more appropriately applied for mortality risk stratification.