Metformin in Dengue With Obesity (MeDO)

August 30, 2023 updated by: Oxford University Clinical Research Unit, Vietnam

Metformin as Adjunctive Therapy in Overweight and Obese Patients With Dengue: an Open-label Safety and Tolerability Trial

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Vietnam
      • Ho Chi Minh City, Vietnam
        • Hospital for Tropical Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • ≥ 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)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control arm
The control group will be formed of 60 overweight or obese dengue patients receiving standard of care
Experimental: Intervention arm
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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events
Time Frame: Up to 30 days after enrollment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fever clearance time
Time Frame: Up to 7 days after enrollment
Time to temperature <37.5 for 2 consecutive days
Up to 7 days after enrollment
Platelet nadir
Time Frame: Up to 7 days after enrollment
Lowest platelet count recorded during admission
Up to 7 days after enrollment
Percentage increase in hematocrit from baseline
Time Frame: Up to 30 days after enrollment
Percentage increase will be calculated from peak result to baseline (baseline is follow-up time-point)
Up to 30 days after enrollment
Percentage change in endothelial and lipid-inflammatory parameters
Time Frame: Up to 30 days after enrollment
Percentage change in parameters such as: VCAM1, ICAM1, leptin, adiponectin, LDL, AMPK levels will be calculated from peak result to baseline (follow-up time-point)
Up to 30 days after enrollment
Changes in virological parameters
Time Frame: Up to 7 days after enrollment
Area under the curve (AUC) of the serial measurements during days 3 - 6 (log10-transformed), time from enrollment to the first undetectable viraemia, or the first negative NS1 measurement will be compared
Up to 7 days after enrollment
Changes in number of immune cells
Time Frame: Up to 30 days after enrollment
Phenotyping CD8/4+T cell and NK cell and T cell exhaustion markers will be assessed
Up to 30 days after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Investigators

  • Principal Investigator: Sophie Yacoub, PhD. MD, University of Oxford, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 27, 2020

Primary Completion (Actual)

June 1, 2023

Study Completion (Actual)

August 1, 2023

Study Registration Dates

First Submitted

April 22, 2020

First Submitted That Met QC Criteria

May 3, 2020

First Posted (Actual)

May 6, 2020

Study Record Updates

Last Update Posted (Estimated)

August 31, 2023

Last Update Submitted That Met QC Criteria

August 30, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 56DX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymised data of this study may be requested for publication by journals. Sharing anonymised data with future similar/suitable studies will be decided by the sponsor, PIs and the authority agency where the data was collected. No identifiable information will be shared with any other person/organisation.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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