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Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes.

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ClinicalTrials.gov Identifier: NCT03765359
Recruitment Status : Recruiting
First Posted : December 5, 2018
Last Update Posted : September 13, 2019
Sponsor:
Collaborators:
Turku University Hospital
Oulu University Hospital
Helsinki University Central Hospital
Central Finland Hospital District
Information provided by (Responsible Party):
Tampere University Hospital

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.

Condition or disease Intervention/treatment Phase
Diabetic Pregnancy Insulin Resistance Type1diabetes Drug: metforminhydrochloride Drug: Placebo Oral Tablet Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: placebo controlled
Primary Purpose: Treatment
Official Title: Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes. A Randomized Double-blind Placebo-controlled Multicenter Study.
Actual Study Start Date : August 5, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Active Comparator: 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.
Drug: metforminhydrochloride
metformin 500 mg tablets and insulin
Other Names:
  • A10BA02
  • Diformin
  • Metformin

Placebo Comparator: 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.
Drug: Placebo Oral Tablet
Placebo tablets mimic metformin 500 mg tablets and insulin




Primary Outcome Measures :
  1. Changes in the insulin need during pregnancy [ Time Frame: from 5-10 gestational weeks until the delivery ]
    The insulin dosage (IU/ml) in two weeks sets


Secondary Outcome Measures :
  1. Blood glucose balance during pregnancy [ Time Frame: from gestational weeks 5 until the delivery ]
    HbA1c (mmol/mol)

  2. Blood glucose balance during pregnancy [ Time Frame: from gestational weeks 5 until the delivery ]
    mean blood glucose (mmol/l) level, standard deviation (SD) and the coefficient of variation of the blood glucose levels

  3. Change in the weight [ Time Frame: from gestational weeks 5 until the delivery ]
    Weight gain (g) during pregnancy

  4. Change in the blood pressure [ Time Frame: from gestational weeks 5 until the delivery ]
    Blood pressure (mmHg)

  5. Incidence of pre-eclampsia [ Time Frame: from gestational weeks 20 until the delivery ]
    Incidence of pre-eclampsia (%)

  6. Incidence hepatogestosis [ Time Frame: from gestational weeks 20 until the delivery ]
    Incidence hepatogestosis (%)

  7. Pregnancy complications [ Time Frame: from gestational weeks 5 until the delivery ]
    Incidence proteinuria (mg/mmol or mg/d)

  8. macrosomia [ Time Frame: from gestational weeks 20 until the delivery ]
    estimated fetal weight in ultrasound (grams)

  9. Pregnancy complications [ Time Frame: 12-22 weeks of gestation ]
    incidence of miscarriage (intrauterine death before 22 weeks of gestation or fetal weigth under 500g) (%)

  10. Pregnancy complications [ Time Frame: 22-40 weeks of gestation ]
    incidence of intrauterine death (intrauterine death after 22 weeks of gestation or fetal weigth over 500g) (%)

  11. Thigh fractional volume ultrasound [ Time Frame: from gestational weeks 20 until delivery ]
    Fetal weight estimation (g) is specified by thigh fractional volume ultrasound program

  12. Rate of the caesarean sections [ Time Frame: The delivery ]
    Rate of the caesarean sections (%)

  13. Labour [ Time Frame: The delivery ]
    rate of spontaneous delivery (%)

  14. Rate of the operative vaginal deliveries [ Time Frame: The delivery ]
    Rate of the operative vaginal deliveries (%)

  15. Rate of the shoulder dystocia [ Time Frame: The delivery ]
    Rate of the shoulder dystocia (%)

  16. Labor complications [ Time Frame: The delivery ]
    rate of induced delivery (%)

  17. Rate of the perineal tears [ Time Frame: The delivery ]
    Rate of the perineal tears (%)

  18. Postpartum bleeding [ Time Frame: The delivery ]
    postpartum bleeding (ml)

  19. Newborn variables (gestational age) [ Time Frame: After the delivery ]
    Rate of the premature deliveries (=deliveries before 37 weeks of gestation) (%)

  20. Newborn variables [ Time Frame: After the delivery ]
    weight of the newborn (g)

  21. Newborn outcome [ Time Frame: After the delivery ]
    Acidosis of the newborn (pH)

  22. Newborn outcome (intensive care) [ Time Frame: After the delivery ]
    The need of NICU (neonatal intensive care unit) treatment (days)

  23. Newborn outcome (hypoglycemia) [ Time Frame: After the delivery ]
    The occurrence of hypoglycemia (=plasma glucose under 2.6mmol/l or usage of iv glucose infusion) (%)

  24. Newborn outcome (Erb's) [ Time Frame: After the delivery ]
    Incidence of the Erb's paresis (%)

  25. Cost benefit calculations (sick leaves) [ Time Frame: from gestational weeks 12 until delivery ]
    The need of sick leaves during pregnancy (days)

  26. Cost benefit calculations (visits to maternity outpatient clinic or internal medicine policlinic) [ Time Frame: 14-40 weeks of gestation ]
    The need of polyclinical controls during pregnancy (number of visits/pregnancy)

  27. Cost benefit calculations (hospitalization) [ Time Frame: 14-40 weeks of gestation ]
    The need of hospitalization during pregnancy (days/pregnancy)

  28. Cost benefit calculations (all outpatient visits after delivery ) [ Time Frame: One year after the delivery ]
    The need of policlinical controls of the diabetic mother after the delivery (number of visits)

  29. Cost benefit calculations (hospitalization after delivery, all departments) [ Time Frame: Up to one year after the delivery ]
    The need of hospitalization of the diabetic mother after the delivery (days)

  30. Cost benefit calculations (all hospitalization of the child) [ Time Frame: Until the age of one year ]
    The need of hospitalization of the child (days)

  31. Cost benefit calculations (all policlinical controls of the child) [ Time Frame: Until the age of one year ]
    The need of policlinical controls of the child (number of visits)

  32. high sensitive-CRP [ Time Frame: 7-10, 26-28 and 34-36 weeks of gestation ]
    high sensitive-CRP (mg/l)

  33. lipids [ Time Frame: 7-10, 26-28 and 34-36 weeks of gestation ]
    cholesterol, high density lipoprotein, low density lipoprotein, triglyserids (mmol/l)

  34. Inflammatory markers [ Time Frame: 7-10, 26-28 and 34-36 weeks of gestation ]
    adiponectin, leptin, resistin, IL-6, TNF-α (pg/ml)



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Study is done during pregnancy
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03765359


Contacts
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Contact: Kati Tihtonen, PhD +3583 311 67855 kati.tihtonen@pshp.fi
Contact: Elina Juuma, MD +358142691811 elina.juuma@fimnet.fi

Locations
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Finland
Central Finland Health Care District Recruiting
Jyväskylä, Finland
Contact: Elina Juuma       elina.juuma@ksshp.fi   
Tampere University Hospital Recruiting
Tampere, Finland
Contact: Kati Tihtonen       kati.tihtonen@pshp.fi   
Sponsors and Collaborators
Tampere University Hospital
Turku University Hospital
Oulu University Hospital
Helsinki University Central Hospital
Central Finland Hospital District
Investigators
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Principal Investigator: Kati Tihtonen, PhD Tampere University Hospital, Tampere University

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Responsible Party: Tampere University Hospital
ClinicalTrials.gov Identifier: NCT03765359     History of Changes
Other Study ID Numbers: Diabetes2017
2016-005031-32 ( EudraCT Number )
First Posted: December 5, 2018    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Tampere University Hospital:
insulin need
diabetic pregnancy
insulin resistance
metformin
Additional relevant MeSH terms:
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Pregnancy in Diabetics
Diabetes Mellitus
Diabetes Mellitus, Type 1
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hyperinsulinism
Pregnancy Complications
Insulin
Insulin, Globin Zinc
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs