Literature DB >> 33083561

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

Nguyet Minh Nguyen1, Ho Quang Chanh1, Dong Thi Hoai Tam1, Nguyen Lam Vuong1, Nguyen Thi Xuan Chau1, Nguyen Van Vinh Chau2, Nguyen Thanh Phong2, Huynh Trung Trieu2, Tai Luong Thi Hue2, Tam Cao Thi2, Trung Dinh The1, Huynh Thi Le Duyen1, Ninh Thi Thanh Van1, Quyen Nguyen Than Ha1, Laura Rivino3, Peter Gallagher4, Nick K Jones5, Ronald B Geskus1,6, Evelyne Kestelyn1,6, Sophie Yacoub1,6.   

Abstract

Background:  Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death.  In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes.  This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity.
Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events.  Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion:  Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses.  Trial registration: ClinicalTrials.gov: NCT04377451 (May 6 th 2020). Copyright:
© 2021 Nguyen NM et al.

Entities:  

Keywords:  Vietnam; clinical trial; dengue; metformin; obesity; therapeutic

Year:  2021        PMID: 33083561      PMCID: PMC7539082.2          DOI: 10.12688/wellcomeopenres.16053.2

Source DB:  PubMed          Journal:  Wellcome Open Res        ISSN: 2398-502X


  45 in total

1.  Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial.

Authors:  Belén Pastor-Villaescusa; M Dolores Cañete; Javier Caballero-Villarraso; Raúl Hoyos; Miriam Latorre; Rocío Vázquez-Cobela; Julio Plaza-Díaz; José Maldonado; Gloria Bueno; Rosaura Leis; Ángel Gil; Ramón Cañete; Concepción M Aguilera
Journal:  Pediatrics       Date:  2017-06-12       Impact factor: 7.124

2.  Activation of AMPK restricts coxsackievirus B3 replication by inhibiting lipid accumulation.

Authors:  Wei Xie; Lei Wang; Qian Dai; Hua Yu; Xiaomei He; Junzhi Xiong; Halei Sheng; Di Zhang; Rong Xin; Yajuan Qi; Fuquan Hu; Shaodong Guo; Kebin Zhang
Journal:  J Mol Cell Cardiol       Date:  2015-06-06       Impact factor: 5.000

3.  The effect of metformin on the efficacy of antiviral therapy in patients with genotype 1 chronic hepatitis C and insulin resistance.

Authors:  Jian-Wu Yu; Li-Jie Sun; Yong-Hua Zhao; Peng Kang; Bing-Zhu Yan
Journal:  Int J Infect Dis       Date:  2012-04-07       Impact factor: 3.623

4.  The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients.

Authors:  Canan Ersoy; Sinem Kiyici; Ferah Budak; Barbaros Oral; Metin Guclu; Cevdet Duran; Hadi Selimoglu; Erdinc Erturk; Ercan Tuncel; Sazi Imamoglu
Journal:  Diabetes Res Clin Pract       Date:  2008-03-21       Impact factor: 5.602

5.  Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity.

Authors:  Heike Nave; Guenter Mueller; Britta Siegmund; Roland Jacobs; Thorsten Stroh; Ulrike Schueler; Matthias Hopfe; Patrick Behrendt; Tobias Buchenauer; Reinhard Pabst; Georg Brabant
Journal:  Endocrinology       Date:  2008-03-20       Impact factor: 4.736

Review 6.  Impact of Obesity and Metabolic Syndrome on Immunity.

Authors:  Catherine J Andersen; Kelsey E Murphy; Maria Luz Fernandez
Journal:  Adv Nutr       Date:  2016-01-15       Impact factor: 8.701

7.  Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial.

Authors:  Anne van Rongen; Marloes P van der Aa; Maja Matic; Ron H N van Schaik; Vera H M Deneer; Marja M van der Vorst; Catherijne A J Knibbe
Journal:  Paediatr Drugs       Date:  2018-08       Impact factor: 3.022

Review 8.  Regulation and function of AMPK in physiology and diseases.

Authors:  Sang-Min Jeon
Journal:  Exp Mol Med       Date:  2016-07-15       Impact factor: 8.718

9.  Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study.

Authors:  Sophie Yacoub; Phung Khanh Lam; Le Hoang Mai Vu; Thi Lien Le; Ngo Thanh Ha; Tran Thi Toan; Nguyen Thu Van; Nguyen Than Ha Quyen; Huynh Thi Le Duyen; Nguyen Van Kinh; Annette Fox; Juthathip Mongkolspaya; Marcel Wolbers; Cameron Paul Simmons; Gavin Robert Screaton; Heiman Wertheim; Bridget Wills
Journal:  J Infect Dis       Date:  2016-05-26       Impact factor: 5.226

10.  Obesity and inflammation: the linking mechanism and the complications.

Authors:  Mohammed S Ellulu; Ismail Patimah; Huzwah Khaza'ai; Asmah Rahmat; Yehia Abed
Journal:  Arch Med Sci       Date:  2016-03-31       Impact factor: 3.318

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  1 in total

1.  The antiviral effect of metformin on zika and dengue virus infection.

Authors:  Carlos Noe Farfan-Morales; Carlos Daniel Cordero-Rivera; Juan Fidel Osuna-Ramos; Irma Eloisa Monroy-Muñoz; Luis Adrián De Jesús-González; José Esteban Muñoz-Medina; Arianna M Hurtado-Monzón; José Manuel Reyes-Ruiz; Rosa María Del Ángel
Journal:  Sci Rep       Date:  2021-04-22       Impact factor: 4.379

  1 in total

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