Metformin as Adjunctive Therapy in Overweight and Obese Patients With Dengue: an Open-label Safety and Tolerability Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Number of adverse events
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Metformin (Drug)
结局指标
主要结局
Number of adverse events
时间窗: 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
次要结局
- 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)
- Changes in number of immune cells(Up to 30 days after enrollment)