Metformin in Dengue With Obesity
Condition: Dengue; Viral Infection; Metformin; Anti-inflammatory Agents; Obesity; Overweight
MeSH terms: Dengue; Virus Diseases; Obesity; Overweight
Study type: Interventional
Phase: Phase 1/Phase 2

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
    

Detailed description: 
      This is an open-label safety and tolerability study investigating the effects of five days of
      metformin treatment. The metformin therapy will be given to eligible participants admitted to
      the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. The 60 patients
      receiving metformin intervention will be compared to 60 age-matched overweight or obese
      controls, who get the standard supportive treatment only.

      The intervention will be conducted in two phases, with a dose escalation. In the initial
      phase (cohort 1), five young adults (16-30 years) and five children (age 10-16 years) with
      body mass index (BMI) >25 kg/m2 (BMI-for-age >1 standard deviation - SD) will be provided
      with a low dose of metformin once daily at 850mg and 500mg respectively. A Data Monitoring
      Committee (DMC) review will take place after day 5 data is fully available for the first ten
      patients enrolled in cohort 1. If the five-day safety and clinical data of cohort 1 show no
      safety concerns, the study will progress to the second phase (cohort 2). This will include 25
      adults and 25 children, who will be given a weight-based dose of metformin; 1000mg (500mg
      twice daily) for participants with weight < 60kg, and 1500mg (1000mg mane, 500mg nocte) for
      those ≥ 60kg.

      Patients that are admitted to the HTD within 72 hours of fever, with clinical suspicion of
      dengue, will be invited to participate in the trial. After giving consent, patients will be
      screened for their eligibility to commence treatment with the trial drug. Blood samples will
      be collected to test for NS1, pregnancy (in all female patients), and AST, ALT and creatinine
      levels. Glucose and lactate levels will be measured using point-of-care (POC) tests.

      All patients will be asked to come back for a final FU visit at around 21-28 days after the
      onset of fever.

      Details of all AEs and SAEs will be recorded on specific forms, together with an assessment
      as to whether the events are likely to have been related to any treatment received. All SAEs
      will be reported promptly to the DMC and ECs according to policy. In cases of discontinuation
      due to AEs, participants will be followed up until the events have resolved or stabilized.
    

Intervention name(s): Metformin
Intervention type(s): Drug
Intervention description(s): 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 MeSH terms: Metformin
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: This is an open-label, two-phase dose escalation trial of metformin in overweight/obese patients with dengue compared to standard of care
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dengue; Obesity; Metformin; Vietnam