Clinical trial NCT03765359: Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes.
Official title: Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes. A Randomized Double-blind Placebo-controlled Multicenter Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Pregnancy
Insulin Resistance
Type1diabetes
Keywords: insulin need
diabetic pregnancy
insulin resistance
metformin
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
Collaborators: name: Turku University Hospital
name: Oulu University Hospital
name: Helsinki University Central Hospital
name: Central Finland Hospital District
First posted: 2018-12-05
Enrollment: 101
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* a pregnancy of a woman with type 1 diabetes.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Changes in the insulin need during pregnancy
timeFrame: from 5-10 gestational weeks until the delivery
Secondary outcomes:
measure: Blood glucose balance during pregnancy HbA1c
timeFrame: from gestational weeks 5 until the delivery
measure: Blood glucose balance during pregnancy AVG, SD, CV
timeFrame: from gestational weeks 5 until the delivery
measure: Change in the weight
timeFrame: from gestational weeks 5 until the delivery
measure: Change in the blood pressure
timeFrame: from gestational weeks 5 until the delivery
measure: Incidence of pre-eclampsia
timeFrame: from gestational weeks 20 until the delivery
measure: Incidence hepatogestosis
timeFrame: from gestational weeks 20 until the delivery
measure: Pregnancy complications
timeFrame: from gestational weeks 5 until the delivery
measure: macrosomia
timeFrame: from gestational weeks 20 until the delivery
measure: Pregnancy complications
timeFrame: 12-22 weeks of gestation
measure: Pregnancy complications
timeFrame: 22-40 weeks of gestation
measure: Thigh fractional volume ultrasound
timeFrame: from gestational weeks 20 until delivery
measure: Rate of the caesarean sections
timeFrame: The delivery
measure: Labour
timeFrame: The delivery
measure: Rate of the operative vaginal deliveries
timeFrame: The delivery
measure: Rate of the shoulder dystocia
timeFrame: The delivery
measure: Labor complications
timeFrame: The delivery
measure: Rate of the perineal tears
timeFrame: The delivery
measure: Postpartum bleeding
timeFrame: The delivery
measure: Newborn variables (gestational age)
timeFrame: After the delivery
measure: Newborn variables
timeFrame: After the delivery
measure: Newborn outcome
timeFrame: After the delivery
measure: Newborn outcome (intensive care)
timeFrame: After the delivery
measure: Newborn outcome (hypoglycemia)
timeFrame: After the delivery
measure: Newborn outcome (Erb's)
timeFrame: After the delivery
measure: Cost benefit calculations (sick leaves)
timeFrame: from gestational weeks 12 until delivery
measure: Cost benefit calculations (visits to maternity outpatient clinic or internal medicine policlinic)
timeFrame: 14-40 weeks of gestation
measure: Cost benefit calculations (hospitalization)
timeFrame: 14-40 weeks of gestation
measure: Cost benefit calculations (all outpatient visits after delivery )
timeFrame: One year after the delivery
measure: Cost benefit calculations (hospitalization after delivery, all departments)
timeFrame: Up to one year after the delivery
measure: Cost benefit calculations (all hospitalization of the child)
timeFrame: Until the age of one year
measure: Cost benefit calculations (all policlinical controls of the child)
timeFrame: Until the age of one year
measure: high sensitive-CRP
timeFrame: 7-10, 26-28 and 34-36 weeks of gestation
measure: lipids
timeFrame: 7-10, 26-28 and 34-36 weeks of gestation
measure: Inflammatory markers
timeFrame: 7-10, 26-28 and 34-36 weeks of gestation
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Jyväskylä
country: Finland
facility: Central Finland Health Care District
city: Oulu
country: Finland
facility: Oulu University hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Tampere University Hospital, Tampere University
name: Kati Tihtonen, PhD
role: PRINCIPAL_INVESTIGATOR
References: