A Phase 0/Phase 1 Trial of Metformin for Premature Infants With Bronchopulmonary Dysplasia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Number of participants who tolerate metformin
研究概览
简要总结
The overall objective of this study is to investigate the role of metformin in decreasing lung injury and promoting lung growth in premature infants. There are two phases to this pilot study. For Phase 0, the goal is to investigate the safety and tolerance of oral metformin in premature who have been diagnosed with bronchopulmonary dysplasia (BPD) at 36-44 weeks gestation. For Phase 1, the goal is to investigate metformin safety and tolerance in extremely premature infants who are 7-30 days old who have an increased risk of BPD. The main questions it aims to answer are:
- how well do older premature infants tolerate metformin?
- how well do younger premature infants tolerate metformin?
详细描述
In Phase 0, there are four groups with different doses of metformin, starting at 5mg/kg/day to a maximum of 25mg/kg/day. Participants will take oral metformin twice a day for 3, 7 or 14 days, depending on which group they are in. In Phase 1, there are four groups with different doses of metformin, starting at 15mg/kg/day to a maximum of 25mg/kg/day. Participants will take oral metformin once a day for 3, 7, or 14 days, depending on what group they are in.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 7 Days 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Birth gestational age of < 29 weeks AND
- •Postnatal age between 8 and 22 weeks AND
- •Diagnosed with BPD at 36 weeks postnatal age
- •Inclusion Criteria Phase 1:
- •Birth gestational age of < 29 weeks, AND
- •Requiring mechanical ventilation or positive pressure support at 7 days postnatal age, AND
- •Postnatal age between 7 and 30 days
排除标准
- •Persistent hypoglycemia
- •Lactic acidosis
- •Feeding intolerance
- •Renal or hepatic dysfunction
- •Active infection
- •Congenital anomalies that preclude feedings
- •Infants whose parents have chosen palliative care
研究组 & 干预措施
Phase 0 - Cohort 1
5mg/kg/day in two divided doses for three days
干预措施: Metformin (open-label) (Drug)
Phase 0 - Cohort 2
10mg/kg/day in two divided doses for three days
干预措施: Metformin (open-label) (Drug)
Phase 0 - Cohort 3
20mg/kg/day in two divided doses for seven days
干预措施: Metformin (open-label) (Drug)
Phase 0 - Cohort 4
25mg/kg/day in two divided doses for 14 days
干预措施: Metformin (open-label) (Drug)
Phase 1 - Cohort 1 Escalation
15mg/kg/day in a single daily dose for three days
干预措施: Metformin (open-label) (Drug)
Phase 1 - Cohort 2 Escalation
25mg/kg/day in a single daily dose for three days
干预措施: Metformin (open-label) (Drug)
Phase 1- Cohort 3 Escalation
10mg/kg/day in a single daily dose for three days
干预措施: Metformin (open-label) (Drug)
Phase 1 - Cohort 4 Expansion
10-25mg/kg/day (dose selected from either Cohort 2 or 3)
干预措施: Metformin (open-label) (Drug)
Phase 1 - Cohort 5 Expansion
10-25mg/kg/day (dose selected from either Cohort 2 or 3)
干预措施: Metformin (open-label) (Drug)
结局指标
主要结局
Number of participants who tolerate metformin
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who receive enteral doses of metformin and complete the study days without an adverse event while continuing enteral feedings
Number of participants with treatment-related adverse events
时间窗: 14 days after administration of the first dose of metformin
Number of participants who develop hypoglycemia defined as blood glucose value \<50
Number of participants with treatment-related metabolic acidosis
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who develop lactic acid levels \> 5mmol/L
Number of subjects with treatment-related feeding problems
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who require a decrease in enteral feeding volume by \>50% from baseline
Number of subjects who require dose adjustments of metformin
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who need decreases in dose or discontinuation of metformin due to hepatic or renal dysfunction
Number of subjects with respiratory deterioration
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who develop pneumonia and increases in oxygen concentration and ventilator support during the study
Number of subjects who complete pharmacokinetic evaluation of metformin
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who have at least one metformin concentration in blood measured at 1, 4 and 12 hours after an enteric dose
Pharmacokinetic analysis of metformin
时间窗: 14 days after administration of the first dose of metformin
Area under the curve of Plasma Concentration Versus Time (AUC) of metformin over a time frame of 1, 4 and 12 hours after an enteric dose of metformin.
Number of subjects who complete the treatment protocol
时间窗: 14 days after administration of the first dose of metformin
Number of subjects who complete the study doses of enteric metformin
次要结局
- Incidence of bronchopulmonary dysplasia(14 days after administration of the first dose of metformin)
- Incidence of necrotizing enterocolitis(14 days after administration of the first dose of metformin)
- Incidence of retinopathy of prematurity(14 days after administration of the first dose of metformin)
- Incidence of intraventricular hemorrhage(14 days after administration of the first dose of metformin)
- Incidence of patent ductus arteriosus(14 days after administration of the first dose of metformin)
研究者
G. Ganesh Konduri
Professor, Division Chief of Neonatology
Medical College of Wisconsin