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

Autor: Nguyen NM; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Chanh HQ; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Tam DTH; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Vuong NL; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Chau NTX; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Chau NVV; Hospital for Tropical Diseases, Ho Chi Minh City, 700000, Vietnam., Phong NT; Hospital for Tropical Diseases, Ho Chi Minh City, 700000, Vietnam., Trieu HT; Hospital for Tropical Diseases, Ho Chi Minh City, 700000, Vietnam., Luong Thi Hue T; Hospital for Tropical Diseases, Ho Chi Minh City, 700000, Vietnam., Cao Thi T; Hospital for Tropical Diseases, Ho Chi Minh City, 700000, Vietnam., Dinh The T; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Duyen HTL; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Van NTT; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Nguyen Than Ha Q; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam., Rivino L; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK., Gallagher P; University of Warwick, Coventry, UK., Jones NK; University of Cambridge, Cambridge, UK., Geskus RB; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam.; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, UK., Kestelyn E; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam.; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, UK., Yacoub S; Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, Vietnam.; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, UK.
Jazyk: angličtina
Zdroj: Wellcome open research [Wellcome Open Res] 2021 Feb 08; Vol. 5, pp. 160. Date of Electronic Publication: 2021 Feb 08 (Print Publication: 2020).
DOI: 10.12688/wellcomeopenres.16053.2
Abstrakt: 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).
Competing Interests: No competing interests were disclosed.
(Copyright: © 2021 Nguyen NM et al.)
Databáze: MEDLINE
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