Efficacy of Metformin in Achieving Glycaemia Goals as Recommended for the Treatment of Gestational Diabetes in Non Obese Women

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Terminated

CT.gov ID

NCT01756105

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

16.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Gestational diabetes (GD) is defined by a hyperglycemia discovered during pregnancy, leading to fetal and maternal complications which may be prevented by reaching very strict glycaemia targets. Prevalence depends on patient's ethnic group and is about 6 to 14%. This prevalence is increasing due to increased GD risk factors (obesity, pregnancy over 35) and also because criteria of screening have been strengthened after the results of last studies. Usual treatment is diet and in case of failure insulin therapy with multiple injections which may lead to hypoglycemia and weight gain and is very difficult to manage for patients. Some studies have shown the comparable effect of metformin and insulin in about 50% of GD obese patients. The aim of our study is to evaluate efficacy of metformin, outcomes in mother and fetus and baby of metformin. In case of metformin failure, insulin will be added in order to obtain glycaemia in desired goals.Oxidative stress will be assessed in mother blood, baby umbilical cord blood, baby umbilical cord and placenta in 90 women and the oxidative stress compared between insulin and metformin alone treated patients.

Condition or Disease	Intervention/Treatment	Phase
Gestational Diabetes Metformin Treatment Oxidative Stress	Drug: Metformin Drug: Rapid acting analog insulin Intermediate acting NPH Insulin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Gestational Diabetes in Non Obese Women and Metformine

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Feb 1, 2018

Actual Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment by Metformin plus insulin if needed Metformin: from 500 mg 2 time per day to 2500 mg per day; with increment of 500 mg every 5 days until abstention of	Drug: Metformin Metformin: from 500 mg 2 time per day to 2500 mg per day; with increment of 500 mg every 5 days until abstention of Drug: Rapid acting analog insulin Intermediate acting NPH Insulin Insulin therapy:If post meal (2 hours after meal) glycaemia is > to 120 mg/dl introduce Insulin rapid acting analog (Humalog, Novorapid) before the meal concerned and according to the weight. If weight is < 80 kg: breakfast 5U, lunch time 3U, and dinner 4U. If weight is > 80 kg :breakast 6U, lunch time 4U, dinner 5U.If post meal glycaemia stay over 120 mg/dl but lower than130 mg/dl: do 1 U more.If post meal glycaemia stay over 140 mg/dl : do 2 UI moreIf fasting glycaemia is over 95 mg/dl : introduce NPH Insulin (Umuline NPH, insulatard) before sleeping : 5U if weight is < 80 kg - 6U if weight is > 80 kgIf fasting glycaemia stay over 95 mg/dl increase NPH Insulin for 1 U and for 2 U if fasting glycaemia is over 110 mg/dl.
Active Comparator: treatment by insulin Insulin therapy:If post meal (2 hours after meal) glycaemia is > to 120 mg/dl introduce Insulin rapid acting analog (Humalog, Novorapid) before the meal concerned and according to the weight. If weight is < 80 kg: breakfast 5U, lunch time 3U, and dinner 4U. If weight is > 80 kg :breakast 6U, lunch time 4U, dinner 5U.If post meal glycaemia stay over 120 mg/dl but lower than130 mg/dl: do 1 U more.If post meal glycaemia stay over 140 mg/dl : do 2 UI moreIf fasting glycaemia is over 95 mg/dl : introduce NPH Insulin (Umuline NPH, insulatard) before sleeping : 5U if weight is < 80 kg - 6U if weight is > 80 kgIf fasting glycaemia stay over 95 mg/dl increase NPH Insulin for 1 U and for 2 U if fasting glycaemia is over 110 mg/dl.	Drug: Rapid acting analog insulin Intermediate acting NPH Insulin Insulin therapy:If post meal (2 hours after meal) glycaemia is > to 120 mg/dl introduce Insulin rapid acting analog (Humalog, Novorapid) before the meal concerned and according to the weight. If weight is < 80 kg: breakfast 5U, lunch time 3U, and dinner 4U. If weight is > 80 kg :breakast 6U, lunch time 4U, dinner 5U.If post meal glycaemia stay over 120 mg/dl but lower than130 mg/dl: do 1 U more.If post meal glycaemia stay over 140 mg/dl : do 2 UI moreIf fasting glycaemia is over 95 mg/dl : introduce NPH Insulin (Umuline NPH, insulatard) before sleeping : 5U if weight is < 80 kg - 6U if weight is > 80 kgIf fasting glycaemia stay over 95 mg/dl increase NPH Insulin for 1 U and for 2 U if fasting glycaemia is over 110 mg/dl.

Arm

Intervention/Treatment

Experimental: treatment by Metformin plus insulin if needed

Metformin: from 500 mg 2 time per day to 2500 mg per day; with increment of 500 mg every 5 days until abstention of

Drug: Metformin

Metformin: from 500 mg 2 time per day to 2500 mg per day; with increment of 500 mg every 5 days until abstention of

Drug: Rapid acting analog insulin Intermediate acting NPH Insulin

Insulin therapy:If post meal (2 hours after meal) glycaemia is > to 120 mg/dl introduce Insulin rapid acting analog (Humalog*, Novorapid*) before the meal concerned and according to the weight. If weight is < 80 kg: breakfast 5U, lunch time 3U, and dinner 4U. If weight is > 80 kg :breakast 6U, lunch time 4U, dinner 5U.If post meal glycaemia stay over 120 mg/dl but lower than130 mg/dl: do 1 U more.If post meal glycaemia stay over 140 mg/dl : do 2 UI moreIf fasting glycaemia is over 95 mg/dl : introduce NPH Insulin (Umuline NPH*, insulatard*) before sleeping : 5U if weight is < 80 kg - 6U if weight is > 80 kgIf fasting glycaemia stay over 95 mg/dl increase NPH Insulin for 1 U and for 2 U if fasting glycaemia is over 110 mg/dl.

Active Comparator: treatment by insulin

Drug: Rapid acting analog insulin Intermediate acting NPH Insulin

Outcome Measures

Primary Outcome Measures

Efficacy of metformin in treatment of gestational diabetes based on capillary glycaemia with an objective of less than 6 measures out of range [After diagnosis of gestational diabetes and until 3 months after delivery; screening made between 22th and 28th week of gestation]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women.

Age more than 18 and less than 40 years.
Unique spontaneous pregnancy.-BMI less than 30kg/m2 before pregnancy.
24 to 30 weeks of amenorrhea or 22 to 28 weeks of gestation.
Gestational diabetes.
Social Security affiliated subject.- Patient able to understand and signed informed consent.

Exclusion Criteria:

Contraindications to metformin.
Metformin treatment prior to protocol inclusion.
Multiple pregnancies.
Diabetes diagnosed prior to pregnancy.
High blood pressure prior to pregnancy.
Pregnancy hepatic complication
High blood pressure prior to study inclusion.
Pre or eclampsia.- Premature membranes rupture.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hôpitaux Civils de Colmar	Colmar	France	68024
2	CHU Dijon,	Dijon	France	21030
3	Centre hospitalier de Mulhouse	Mulhouse	France	68070
4	CHU de Reims	Reims	France	51092
5	Hôpitaux Universitaires de Strasbourg	Strasbourg	France	67091