Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations]
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...
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| Format: | Article |
| Language: | English |
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Wellcome
2020-07-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/5-160/v1 |
| _version_ | 1818256606650957824 |
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| author | Nguyet Minh Nguyen Ho Quang Chanh Dong Thi Hoai Tam Nguyen Lam Vuong Nguyen Thi Xuan Chau Nguyen Van Vinh Chau Nguyen Thanh Phong Huynh Trung Trieu Tai Luong Thi Hue Tam Cao Thi Trung Dinh The Huynh Thi Le Duyen Ninh Thi Thanh Van Quyen Nguyen Than Ha Laura Rivino Peter Gallagher Nick K. Jones Ronald B. Geskus Evelyne Kestelyn Sophie Yacoub |
| author_facet | Nguyet Minh Nguyen Ho Quang Chanh Dong Thi Hoai Tam Nguyen Lam Vuong Nguyen Thi Xuan Chau Nguyen Van Vinh Chau Nguyen Thanh Phong Huynh Trung Trieu Tai Luong Thi Hue Tam Cao Thi Trung Dinh The Huynh Thi Le Duyen Ninh Thi Thanh Van Quyen Nguyen Than Ha Laura Rivino Peter Gallagher Nick K. Jones Ronald B. Geskus Evelyne Kestelyn Sophie Yacoub |
| author_sort | Nguyet Minh Nguyen |
| collection | DOAJ |
| description | 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 6th 2020). |
| first_indexed | 2024-12-12T17:30:26Z |
| format | Article |
| id | doaj.art-7455192305464eb3bbf777690aee4c38 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-12T17:30:26Z |
| publishDate | 2020-07-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-7455192305464eb3bbf777690aee4c382022-12-22T00:17:24ZengWellcomeWellcome Open Research2398-502X2020-07-01510.12688/wellcomeopenres.16053.117609Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations]Nguyet Minh Nguyen0Ho Quang Chanh1Dong Thi Hoai Tam2Nguyen Lam Vuong3Nguyen Thi Xuan Chau4Nguyen Van Vinh Chau5Nguyen Thanh Phong6Huynh Trung Trieu7Tai Luong Thi Hue8Tam Cao Thi9Trung Dinh The10Huynh Thi Le Duyen11Ninh Thi Thanh Van12Quyen Nguyen Than Ha13Laura Rivino14Peter Gallagher15Nick K. Jones16Ronald B. Geskus17Evelyne Kestelyn18Sophie Yacoub19Oxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamHospital for Tropical Diseases, Ho Chi Minh City, 700000, VietnamHospital for Tropical Diseases, Ho Chi Minh City, 700000, VietnamHospital for Tropical Diseases, Ho Chi Minh City, 700000, VietnamHospital for Tropical Diseases, Ho Chi Minh City, 700000, VietnamHospital for Tropical Diseases, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, UKUniversity of Warwick, Coventry, UKUniversity of Cambridge, Cambridge, UKOxford University Clinical Research Unit, Ho Chi Minh City, 700000, VietnamCentre for Tropical Medicine and Global Health, Oxford University, Oxford, UKCentre for Tropical Medicine and Global Health, Oxford University, Oxford, UKBackground: 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 6th 2020).https://wellcomeopenresearch.org/articles/5-160/v1 |
| spellingShingle | Nguyet Minh Nguyen Ho Quang Chanh Dong Thi Hoai Tam Nguyen Lam Vuong Nguyen Thi Xuan Chau Nguyen Van Vinh Chau Nguyen Thanh Phong Huynh Trung Trieu Tai Luong Thi Hue Tam Cao Thi Trung Dinh The Huynh Thi Le Duyen Ninh Thi Thanh Van Quyen Nguyen Than Ha Laura Rivino Peter Gallagher Nick K. Jones Ronald B. Geskus Evelyne Kestelyn Sophie Yacoub Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] Wellcome Open Research |
| title | Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] |
| title_full | Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] |
| title_fullStr | Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] |
| title_full_unstemmed | Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] |
| title_short | Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO) [version 1; peer review: 2 approved, 1 approved with reservations] |
| title_sort | metformin as adjunctive therapy for dengue in overweight and obese patients a protocol for an open label clinical trial medo version 1 peer review 2 approved 1 approved with reservations |
| url | https://wellcomeopenresearch.org/articles/5-160/v1 |
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