Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes. A Randomized Double-blind Placebo-controlled Multicenter Study.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 5
- 主要终点
- Changes in the insulin need during pregnancy
研究概览
简要总结
The study investigates whether additional metformin medication in combination with regular insulin treatment will decrease the need of insulin for women with diabetes mellitus type 1 during pregnancy.
详细描述
Insulin resistance during pregnancy of diabetes mellitus type 1 patients (DM1) increases the need for insulin and makes it more difficult to maintain normoglycemia. Fetal exposure to hyperglycemia induces macrosomia which increases fetal and neonatal morbidity and mortality. Further more obesity and excess weight gain during pregnancy enhances insulin resistance and it's an independent risk factor for fetal macrosomia.
Metformin is a medical treatment for type 2 diabetes (DM2) where consequential pathophysiology includes insulin resistance. It reduces hepatic glucose production and enhances the use of glucose in muscles relieving insulin resistance. Metformin has also found to inhibit weight gain effectively.
Metformin has approved to be safe and effective in patients with gestational diabetes (GDM). It has found to reduce weight gain and improve postprandial blood glucose levels during pregnancy and reduce neonatal birth trauma in GDM. However, there are no previous studies about the use of metformin in pregnant women with DM1.
Two hundred women with DM1 will be randomized to get placebo or metformin in addition to regular insulin treatment. The sample size has been estimated to demonstrate the difference of 15 % in the need to increase insulin dosages during the pregnancy between the study groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
placebo controlled
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •a pregnancy of a woman with type 1 diabetes.
排除标准
- •multiple pregnancy, significant underlying disease (hearth disease, kidney transplant, IBD (inflammatory bowel disease ), SLE (systemic lupus erythematosus ), diseases with use of high dosage corticosteroids (severe asthma or rheumatic disease), severe complications of diabetes (nephropathy, neuropathy, gastroparesis or severe retinopathy), substance abuse, smoking, BMI <18, strong early pregnancy nausea (=hyperemesis)
研究组 & 干预措施
metforminhydrochloride
Metformin medication starts on 12-14 weeks of gestation. The starting dosage is 1 tablet (500 mg) x1 and it is increased gradually 1 tablet a week up to 2+2 tablets (2000mg) daily. Duration of the treatment is approximately until one week before delivery. Otherwise metformin treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines.
干预措施: metforminhydrochloride (Drug)
Placebo Oral Tablet
Placebo tablets starts on 12-14 weeks of gestation. The starting dosage is 1 tablet x1 and it is increased gradually 1 tablet a week up to 2+2 tablets daily. Duration of the treatment is approximately until one week before delivery. Otherwise placebo treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Changes in the insulin need during pregnancy
时间窗: from 5-10 gestational weeks until the delivery
The insulin dosage (IU/ml) in two weeks sets
次要结局
- Newborn outcome(After the delivery)
- Blood glucose balance during pregnancy HbA1c(from gestational weeks 5 until the delivery)
- Change in the weight(from gestational weeks 5 until the delivery)
- Rate of the operative vaginal deliveries(The delivery)
- Newborn variables (gestational age)(After the delivery)
- Incidence hepatogestosis(from gestational weeks 20 until the delivery)
- macrosomia(from gestational weeks 20 until the delivery)
- Rate of the caesarean sections(The delivery)
- Rate of the shoulder dystocia(The delivery)
- Rate of the perineal tears(The delivery)
- Newborn variables(After the delivery)
- Postpartum bleeding(The delivery)
- Cost benefit calculations (hospitalization)(14-40 weeks of gestation)
- Blood glucose balance during pregnancy AVG, SD, CV(from gestational weeks 5 until the delivery)
- Change in the blood pressure(from gestational weeks 5 until the delivery)
- Incidence of pre-eclampsia(from gestational weeks 20 until the delivery)
- Pregnancy complications(22-40 weeks of gestation)
- Thigh fractional volume ultrasound(from gestational weeks 20 until delivery)
- Labour(The delivery)
- Labor complications(The delivery)
- Newborn outcome (hypoglycemia)(After the delivery)
- Cost benefit calculations (all policlinical controls of the child)(Until the age of one year)
- high sensitive-CRP(7-10, 26-28 and 34-36 weeks of gestation)
- Newborn outcome (intensive care)(After the delivery)
- Newborn outcome (Erb's)(After the delivery)
- Cost benefit calculations (sick leaves)(from gestational weeks 12 until delivery)
- Cost benefit calculations (visits to maternity outpatient clinic or internal medicine policlinic)(14-40 weeks of gestation)
- Cost benefit calculations (all outpatient visits after delivery )(One year after the delivery)
- Cost benefit calculations (hospitalization after delivery, all departments)(Up to one year after the delivery)
- lipids(7-10, 26-28 and 34-36 weeks of gestation)
- Cost benefit calculations (all hospitalization of the child)(Until the age of one year)
- Inflammatory markers(7-10, 26-28 and 34-36 weeks of gestation)