A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Recruitment feasibility
研究概览
简要总结
Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Months 至 6 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •<6 months old at time of enrollment, and able to initiate study drug between 3 and 6 months old.
- •Born > 35 weeks gestational age with a clinical diagnosis of HIE at birth, who receive therapeutic hypothermia.
- •Post-hypothermia brain MRI with evidence of hypoxic-ischemic brain injury, based on the neuroradiology clinical report. Specifically, participants must have had evidence of a lactate peak by magnetic resonance spectroscopy and/or signal abnormalities by conventional (T1 and/or T2) or diffusion-weighted images consistent with hypoxic-ischemic pattern of injury.
- •English- or Spanish-speaking families, as the parents/guardians will be responsible for documenting dose administrations and adverse events.
排除标准
- •Known genetic or chromosomal disorder, and in the presence of congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator (PI) or delegate, affect drug metabolism.
- •Maternal use of metformin while actively breastfeeding.
- •Infant weight below the 10th percentile based on WHO growth charts at the time of study drug initiation.
- •Normal post-hypothermia brain MRI, without evidence of ischemic brain injury, based on the neuroradiology clinical report.
- •Concomitant use of the following drugs: anti-diabetic drugs (insulin, sulfonylureas), steroids, diuretics (furosemide, chlorothiazide, spironolactone), diazoxide, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers (including nifedipine), phenytoin, valproic acid, topiramate, cimetidine, corticosteroids, thyroid medications, sympathomimetics, carbonic anhydrase inhibitors, or any antibiotics.
- •Any condition or diagnosis, that could in the opinion of the PI or delegate, interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk.
研究组 & 干预措施
Metformin Intervention
Participants will complete a pre-study visit with baseline bloodwork including a complete blood count (CBC), liver and renal function, basic chemistry, glucose, and lactate. At this visit, parents will be taught how to administer metformin and given a 6-week supply (at 25% & 50% of the target dose for three weeks each) to minimize potential gastrointestinal upset. Parents will be educated on adverse effects and receive a diary to log dose administration and side effects. They will also be asked to perform at-home glucometer checks twice daily for 3 days post the dose escalation. After six weeks, participants will return for a study visit with repeat labs including assessing the levels of vitamin B12 and plasma metformin for measurement of pharmacokinetics. Parents will then receive a 6-week supply of metformin at the full dose (~32mg/kg) for 6 weeks. A final study visit will then occur following 12-weeks of metformin therapy, with repeat labs including plasma metformin levels.
干预措施: Metformin (Drug)
结局指标
主要结局
Recruitment feasibility
时间窗: 12 weeks
To assess feasibility, the number of eligible patients will be compared to the number of patients who consent to participate in the study.
Safety profile of kidney function
时间窗: 12 weeks
A renal function panel (chem 10 with renal function) will be performed prior to the initiation of therapy and at all subsequent study visits.
Safety profile of liver function
时间窗: 12 weeks
A liver function test (LFT) will be performed prior to the initiation of therapy and at all subsequent study visits.
次要结局
- Validity of neonatal model of metformin pharmacokinetics(12 weeks)
研究者
Brian Kalish
Neonatologist, Assistant Professor of Pediatrics
Boston Children's Hospital