Metformin in Dengue With Obesity

NCT04377451 | Completed Phase 1 DMC

• 1 other identifier: 56DX
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the effect of metformin as host-directed therapy in obese/overweight patients with dengue Primary Objective To evaluate the safety and tolerability of metformin in obese/overweight young adults and children with dengue Secondary Objectives

• To assess the effect of metformin therapy in obese/overweight patients with dengue on physiological, clinical and virological parameters
• To assess the immunomodulation effects of metformin therapy in obese/overweight patients with dengue
• To assess difference in gene expression between treatment group compared to non-treatment population

Conditions

Dengue; Viral Infection; Metformin; Anti-inflammatory Agents; Obesity; Overweight

Keywords

Dengue; Obesity; Metformin; Vietnam

Outcome Measures

Primary Outcomes (1)

• Number of adverse events

  Number of severe clinical symptoms and signs, including severe diarrhoea (defined as \>5 episodes watery stool/day), severe vomiting (\>=3 episodes separated by 15 minutes/24 hours), severe abdominal pain and laboratory markers of severity including -Hypoglycaemia defined as glucose \<3.9 mmol/l, Hyperlactatemia (lactate \>3 mmol/l), ALT/AST \>400 U/l

  Up to 30 days after enrollment

Secondary Outcomes (6)

• Fever clearance time

  Up to 7 days after enrollment

• Platelet nadir

  Up to 7 days after enrollment

• Percentage increase in hematocrit from baseline

  Up to 30 days after enrollment

• Percentage change in endothelial and lipid-inflammatory parameters

  Up to 30 days after enrollment

• Changes in virological parameters

  Up to 7 days after enrollment

Study Arms (2)

Control arm

NO INTERVENTION

The control group will be formed of 60 overweight or obese dengue patients receiving standard of care

Intervention arm

EXPERIMENTAL

Two cohorts receive a 5-day course of metformin treatment. In the initial phase (cohort 1), 5 young adults and 5 children (age \<16) will receive a low dose of metformin. In the second phase (cohort 2), 25 adult and 25 paediatric patients will receive a weight-based dose of metformin.

Drug: Metformin

Interventions

Metformin DRUG

The trial will be conducted in two phases, with a dose escalation of metformin. Metformin dosing will begin at 500mg (children) and 850mg (adults) once daily for 5 days in cohort 1. Cohort 2 will be received weight-based doses; 5 days of 1000mg (500mg twice daily) for those weighing \<60kg and 5 days of 1500mg (1000mg mane, 500mg nocte) for those weighing ≥60kg

Intervention arm

Eligibility Criteria

• Age: 10 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≥ 10 years to ≤ 30 years of age,
• Clinical diagnosis of dengue (based on WHO 2009 Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control/Vietnam Ministry of Health 2019: Guidelines for Dengue Diagnosis, treatment and prevention)
• Positive NS1 rapid test
• ≤ 3 days (≤ 72 hours) of fever
• BMI \> 25 Kg/m2 (or BMI-for-age \> 1 SD);
• Written informed consent or assent to participate in the study
• Agree to come back for follow up visit around day 21-28 of illness (maximum 1 month)

You may not qualify if:

• In all female patients: Pregnancy Localizing features suggesting an alternative diagnosis, e.g. pneumonia, otitis etc.
• History of hypersensitivity to metformin
• Severe infection, including: (1) severe dengue (dengue shock syndrome, severe haemorrhage, severe organ impairment) (2) central nervous system infection, or (3) septicaemia etc…
• Baseline lactate level \> 2.0 mmol/L
• Baseline glucose level \< 3.9 mmol/L OR \< 70 mg/dL
• Already taking metformin or any other regular hypoglycaemic agents, eg. insulin
• Significant diarrhoea and/or vomiting (\> 3 episodes in 24 hours)
• Have acute or chronic renal impairment (baseline GFR \< 30ml/min)
• Liver impairment (baseline AST and ALT \> 250 U/L)
• Being treated for heart failure or have had a recent heart attack (in the last year)
• Taking any drug with significant interaction with metformin
• The study physician judges that the patient is unlikely to attend follow up visit at around 3-4 weeks after fever onset - e.g. due to long travelling distance from the clinic

Sponsors & Collaborators

• Oxford University Clinical Research Unit, Vietnam: lead
• Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam: collaborator

Study Sites (1)

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Location

Related Publications (14)

• Do LM, Tran TK, Eriksson B, Petzold M, Nguyen CT, Ascher H. Preschool overweight and obesity in urban and rural Vietnam: differences in prevalence and associated factors. Glob Health Action. 2015 Oct 8;8:28615. doi: 10.3402/gha.v8.28615. eCollection 2015.

  PMID: 26452338 BACKGROUND

• Dieu HT, Dibley MJ, Sibbritt DW, Hanh TT. Trends in overweight and obesity in pre-school children in urban areas of Ho Chi Minh City, Vietnam, from 2002 to 2005. Public Health Nutr. 2009 May;12(5):702-9. doi: 10.1017/S1368980008003017. Epub 2008 Jul 29.

  PMID: 18664311 BACKGROUND

• Nguyen PV, Hong TK, Hoang T, Nguyen DT, Robert AR. High prevalence of overweight among adolescents in Ho Chi Minh City, Vietnam. BMC Public Health. 2013 Feb 15;13:141. doi: 10.1186/1471-2458-13-141.

  PMID: 23414441 BACKGROUND

• Zulkipli MS, Dahlui M, Jamil N, Peramalah D, Wai HVC, Bulgiba A, Rampal S. The association between obesity and dengue severity among pediatric patients: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2018 Feb 7;12(2):e0006263. doi: 10.1371/journal.pntd.0006263. eCollection 2018 Feb.

  PMID: 29415036 BACKGROUND

• Harris K, Smith L. Safety and efficacy of metformin in patients with type 2 diabetes mellitus and chronic hepatitis C. Ann Pharmacother. 2013 Oct;47(10):1348-52. doi: 10.1177/1060028013503108.

  PMID: 24259699 BACKGROUND

• Doyle MA, Singer J, Lee T, Muir M, Cooper C. Improving treatment and liver fibrosis outcomes with metformin in HCV-HIV co-infected and HCV mono-infected patients with insulin resistance: study protocol for a randomized controlled trial. Trials. 2016 Jul 20;17(1):331. doi: 10.1186/s13063-016-1454-6.

  PMID: 27439433 BACKGROUND

• Htun HL, Yeo TW, Tam CC, Pang J, Leo YS, Lye DC. Metformin Use and Severe Dengue in Diabetic Adults. Sci Rep. 2018 Feb 20;8(1):3344. doi: 10.1038/s41598-018-21612-6.

  PMID: 29463812 BACKGROUND

• Khan IM, Malik BR, Randhawa FA, Butt NF, Malik U, Hamid S. Comparison of metformin and pioglitazone in achieving sustained virological response in chronic hepatitis C patients with insulin resistance: A quasi-experimental study. J Pak Med Assoc. 2017 Dec;67(12):1848-1852.

  PMID: 29256528 BACKGROUND

• Padmapriyadarsini C, Bhavani PK, Natrajan M, Ponnuraja C, Kumar H, Gomathy SN, Guleria R, Jawahar SM, Singh M, Balganesh T, Swaminathan S. Evaluation of metformin in combination with rifampicin containing antituberculosis therapy in patients with new, smear-positive pulmonary tuberculosis (METRIF): study protocol for a randomised clinical trial. BMJ Open. 2019 Mar 1;9(3):e024363. doi: 10.1136/bmjopen-2018-024363.

  PMID: 30826761 BACKGROUND

• Kay JP, Alemzadeh R, Langley G, D'Angelo L, Smith P, Holshouser S. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism. 2001 Dec;50(12):1457-61. doi: 10.1053/meta.2001.28078.

  PMID: 11735093 BACKGROUND

• Pastor-Villaescusa B, Canete MD, Villarraso-Caballero J, et al. Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial. Pediatrics. 2017;140 (1):e20164285. Pediatrics. 2017 Nov;140(5):e20172555. doi: 10.1542/peds.2017-2555. No abstract available.

  PMID: 29089408 BACKGROUND

• Soto-Acosta R, Bautista-Carbajal P, Cervantes-Salazar M, Angel-Ambrocio AH, Del Angel RM. DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target. PLoS Pathog. 2017 Apr 6;13(4):e1006257. doi: 10.1371/journal.ppat.1006257. eCollection 2017 Apr.

  PMID: 28384260 BACKGROUND

• Minh Nguyen N, Thi Hoai Tam D, Quang Chanh H, Trung Trieu H, Thi Xuan Chau N, Thanh Van N, Thanh Phong N, Thi Tam C, Thi Hong Lan N, Thi Hue Tai L, Thi Cam Huong N, Thi Ngoc Thuan L, Van Hao N, Tu Qui P, Thi Dong Vien T, Thi Hai Men P, Thi Thuy Hoa H, Vinh Tho P, Thi Le Duyen H, Tran Thuy V, Dang Trong T, Tan Thanh Kieu N, McBride A, Kestelyn E, Geskus RB, Lam Vuong N, Yacoub S. Safety and tolerability of metformin in overweight and obese patients with dengue: An open-label clinical trial (MeDO). PLoS Negl Trop Dis. 2025 Jul 1;19(7):e0013281. doi: 10.1371/journal.pntd.0013281. eCollection 2025 Jul.

  PMID: 40591696 DERIVED

• Nguyen NM, Chanh HQ, Tam DTH, Vuong NL, Chau NTX, Chau NVV, Phong NT, Trieu HT, Luong Thi Hue T, Cao Thi T, Dinh The T, Duyen HTL, Van NTT, Nguyen Than Ha Q, Rivino L, Gallagher P, Jones NK, Geskus RB, Kestelyn E, Yacoub S. Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO). Wellcome Open Res. 2021 Feb 8;5:160. doi: 10.12688/wellcomeopenres.16053.2. eCollection 2020.

  PMID: 33083561 DERIVED

MeSH Terms

Conditions

Dengue; Virus Diseases; Obesity; Overweight

Interventions

Metformin

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Sophie Yacoub, PhD. MD

  University of Oxford, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open-label, two-phase dose escalation trial of metformin in overweight/obese patients with dengue compared to standard of care

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: May 6, 2020
• Study Start: July 27, 2020
• Primary Completion: June 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

VN (1)