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DenguePhase 1/2MeDONCT04377451

Metformin in Dengue With Obesity

A Phase 1/2 study testing Metformin in people with Dengue and Viral Infection, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 10 to 30 years
Conditions the study is for
Dengue, Viral Infection, Metformin
What is being tested?
Metformin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteVietnam
Study dates
27 Jul 2020to 1 Aug 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • ≥ 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Vietnam1 site

  • Hospital for Tropical Diseases

    Ho Chi Minh City

Other trials in Vietnam

About this study

Official title: 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
Read the 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.

Being tested
Metformin
Keywords
Dengue, Obesity, Metformin, Vietnam
Medical subject headings
Dengue, Virus Diseases, Obesity, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    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

Study groups in NCT04377451
Study groupRoleWhat they receive
Control armNo interventionThe control group will be formed of 60 overweight or obese dengue patients receiving standard of care
Intervention armExperimentalTwo 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.
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 30 days after enrollment

Secondary outcomes (6)

  1. Fever clearance time

    Time to temperature <37.5 for 2 consecutive days

    Measured: Up to 7 days after enrollment

  2. Platelet nadir

    Lowest platelet count recorded during admission

    Measured: Up to 7 days after enrollment

  3. Percentage increase in hematocrit from baseline

    Percentage increase will be calculated from peak result to baseline (baseline is follow-up time-point)

    Measured: Up to 30 days after enrollment

  4. Percentage change in endothelial and lipid-inflammatory parameters

    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)

    Measured: Up to 30 days after enrollment

  5. Changes in virological parameters

    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

    Measured: Up to 7 days after enrollment

  6. Changes in number of immune cells

    Phenotyping CD8/4+T cell and NK cell and T cell exhaustion markers will be assessed

    Measured: Up to 30 days after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2020
  2. Study start27 Jul 2020
  3. Primary completion1 Jun 2023
  4. Study completion1 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
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)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04377451
Sponsor's protocol ID
56DX
Acronym
MeDO
Status last verified
Aug 2023
First submitted
22 Apr 2020
Last updated
31 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 26452338

  • 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.

    PubMed 18664311

  • 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.

    PubMed 23414441

  • 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.

    PubMed 29415036

  • 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.

    PubMed 24259699

  • 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.

    PubMed 27439433

  • 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.

    PubMed 29463812

  • 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.

    PubMed 29256528

  • 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.

    PubMed 30826761

  • 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.

    PubMed 11735093

  • 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.

    PubMed 29089408

  • 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.

    PubMed 28384260

  • 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.

    PubMed 40591696

  • 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.

    PubMed 33083561

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Metformin in people with Dengue and Viral Infection, run by Oxford University Clinical Research Unit, Vietnam at 1 site in Vietnam.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of adverse events (time frame: Up to 30 days after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04377451, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.

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Metformin in Dengue With Obesity (NCT04377451) | AzTrials