Introduction: Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome phenotype in the liver and thus obviously associated with metabolic abnormalities, including insulin resistance-related to hyperglycaemic and hyperlipidaemia. The prevalence of NAFLD is increasing worldwide. However, currently, there is no consensus regarding the efficacy and safety of drugs used to treat patients with NAFLD/non-alcoholic steatohepatitis (NASH). Guanabenz acetate, a selective α2-adrenoceptor stimulator used in the treatment of hypertension, binds at a high-affinity constant to a nuclear transcriptional coregulator, helicase with zinc finger 2 (Helz2) and inhibits Helz2-medaited steatosis in the liver; chronic oral administration of guanabenz acetate produces a dose-dependent inhibition of lipid accumulation by inhibiting lipogenesis and activating fatty acid Β-oxidation in the liver of obese mice, resulting in improvement of insulin resistance and hyperlipidaemia. Taken all together, guanabenz acetate has a potentially effective in improving the development of NAFLD/NASH and metabolic abnormalities. In this randomised, open label, parallel-group, phase IIa study, we made attempts to conduct a proof-of-concept assessment by evaluating the efficacy and safety of guanabenz acetate treatment in patients with NAFLD/NASH.
Methods And Analysis: A total of 28 adult patients with NAFLD or NASH and hypertension complications meeting the inclusion/exclusion criteria will be enrolled. Patients will be randomised to receive either 4 or 8 mg guanabenz acetate (n=14 per group). Blood tests and MRI will be performed 16 weeks after commencement of treatment. The primary endpoint will be the percentage reduction in hepatic fat content (%) measured using MRI-proton density fat fraction from baseline by at least 3.46% at week 16 after treatment initiation.
Ethics And Dissemination: Ethics approval was obtained from the Ethics Committee of Yokohama City University Hospital before participant enrolment (YCU021001). The results of this study will be submitted for publication in international peer-reviewed journals, and the key findings will be presented at international scientific conferences. Participants wishing to know the results of this study will be contacted directly on data publication.
Trial Registration Number: This trial is registered with ClinicalTrials.gov (number: NCT05084404).
Protocol Version: V.1.1, 19 August 2021.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277396 | PMC |
| http://dx.doi.org/10.1136/bmjopen-2021-060335 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Association between alpha blocker use and the risk of fractures in patients with chronic kidney disease: a cohort study.
BMC Nephrol
December 2024
Department of Nephrology, Graduate School of Medicine, Nagoya University, Tsurumai-Cho 65, Showa-Ku, Nagoya City, Aichi Prefecture, Japan.
Article Synopsis
- Alpha blockers (ABs) are commonly given to patients with chronic kidney disease (CKD) who often deal with high blood pressure, but the link between ABs and fracture risk is unclear, prompting this study.
- The research analyzed a large cohort from a Japanese medical database, focusing on patients newly prescribed either ABs for hypertension or non-AB antihypertensive medications, with separate analyses for males and females.
- The findings showed that while males had no increased fracture risk with AB use, females using ABs for voiding dysfunction exhibited a significant rise in fracture risk compared to those on antihypertensive ABs.
Unlocking the secrets of trace amine-associated receptor 1 agonists: new horizon in neuropsychiatric treatment.
Front Psychiatry
October 2024
Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
For over seven decades, dopamine receptor 2 (D receptor) antagonists remained the mainstay treatment for neuropsychiatric disorders. Although it is effective for treating hyperdopaminergic symptoms, it is often ineffective for treating negative and cognitive deficits. Trace amine-associated receptor 1 (TAAR1) is a novel, pharmacological target in the treatment of schizophrenia and other neuropsychiatric conditions.
View Article and Find Full Text PDFGuanabenz acetate, an antihypertensive drug repurposed as an inhibitor of biofilm.
Microbiol Spectr
November 2024
Biotechnology and Food Engineering Program; and Key Laboratory of Science and Engineering for Health and Medicine of Guangdong Higher Education Institutes, Guangdong Technion-Israel Institute of Technology, Shantou, China.
Unlabelled: Biofilms formed by are composed of amyloid curli and cellulose and have been shown to be linked to pathogenicity, antibiotic resistance, and chronic infections. Guanabenz acetate (GABE), an antihypertensive drug, was identified as a potential strategic repurposing drug due to its biofilm inhibitory properties following an extensive antimicrobial screening assay of 2,202 Food and Drug Administration-approved non-antibiotic agents. The results of this study provide insights into the effectiveness of GABE as a therapeutic alternative against biofilm-associated infectious diseases.
View Article and Find Full Text PDFFramework for Multistakeholder Patient Registries in the Field of Rare Diseases: Focus on Neurogenetic Diseases.
Neurology
September 2024
From the Department of Child Neurology (D.H.S., M.S.v.d.K., N.I.W.), Emma's Children's Hospital, Amsterdam UMC location Vrije Universiteit; Amsterdam Leukodystrophy Center (D.H.S., M.S.v.d.K., N.I.W.), Amsterdam Neuroscience, Cellular & Molecular Mechanisms; Medicine for Society (D.H.S., S.v.d.B., N.R., C.E.M.H.), Platform at Amsterdam UMC location University of Amsterdam; Department of Endocrinology and Metabolism (S.v.d.B., A.B., M.R.D., N.R., C.E.M.H.), Amsterdam UMC location University of Amsterdam; National Health Care Institute (Zorginstituut Nederland) (L.T.), Diemen, the Netherlands; Division of Child Neurology (L.A.A.), Children's Hospital of Philadelphia, PA; Institute of Systems Motor Science (T.B.), CBBM, Universität of Lübeck; Centre of Rare Diseases (T.B.), University Hospital Schleswig Holstein, Lübeck, Germany; Division of Metabolic Diseases (A.B.), Department of Pediatrics, Emma Childrens' Hospital, Amsterdam UMC location University of Amsterdam, the Netherlands; National Health Care Institute RIZIV-INAMI (M.v.d.C.), Brussels, Belgium; VKS (H.D.), Dutch Patient Organization for Metabolic Diseases, Zwolle; United for Metabolic Diseases (UMD) (H.D.), Amsterdam, the Netherlands; International Niemann-Pick Disease Registry (C.D.), Washington, Tyne & Wear, United Kingdom; VSOP-Patient Alliance for Rare and Genetic Diseases (M.H.E.D.), Soest, the Netherlands; Institute for Medical Genetics and Applied Genomics (H.G.), University of Tübingen; Centre for Rare Disease (H.G.), University Hospital Tübingen, Germany; Yaya foundation for 4H Leukodystrophy (V.G.), Minneapolis, MN; Orphanet (T.H.), INSERM US14 Rare Disease Platform, Paris, France; Department of Neurology (G.U.H.), LMU University Hospital, Ludwig-Maximilians-Universität (LMU), Munich; German Center for Neurodegenerative Diseases e.V. (DZNE) (G.U.H., T.K.), Munich; Munich Cluster for Systems Neurology (SyNergy) (G.U.H.), Germany; Department of Pediatrics (H.v.d.H.), Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Sophia Children's Hospital, Rotterdam; European Medicines Agency (C.J., K.P.), Amsterdam; Medicines Evaluation Board (C.J.), Utrecht; Department of Endocrinology and Metabolism (M.L.), Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, University of Amsterdam, the Netherlands; Canadian Agency for Drugs and Health Technology Technologies Agendcy in Health (CADTH) (L.J.L.), Ottawa, Ontario, Canada; CHDI Management, Inc. (E.N.), the company that manages the scientific activities of CHDI Foundation, Inc., New York, NY; National Health Care Institute (M.N., W.G.G.), Diemen, the Netherlands; Department of Neurology (T.K.), University of Bonn, Germany; Department of Integrative Neurophysiology (M.S.v.d.K.), Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, the Netherlands; European Commission (A.P.), Joint Research Centre (JRC), Ispra, Italy; Patient Advocate Organization 'Vereniging HCHWA-d' (HCHWA-D Association) (S.v.R.), the Netherlands; European Leukodystrophies Association (E.F.S.-V.), Paris, France; Medical BioSciences Department (B.d.S.V.), Radboud University Medical Center, Nijmegen; and WHO Collaborating Centre for Pharmaceutical Policy and Regulation (W.G.G.), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, the Netherlands.
Article Synopsis
- Progress in genetic diagnosis and orphan drug legislation has led to new therapies for rare neurogenetic diseases (RNDs), but challenges remain in academia, regulation, and finances.
- The study aims to create a practical framework for developing patient registries that address these challenges and enhance outcomes in care, research, and drug development for RNDs.
- A comprehensive approach combining literature review, interviews with existing registries, and feedback from various stakeholders was used to ensure the framework meets diverse needs and emphasizes key principles like accessible, independent, and trustworthy data governance.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!