Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus

Sponsor

Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health (Other)

Overall Status

Unknown status

CT.gov ID

NCT03610178

Collaborator

(none)

850

Enrollment

Location

Arms

Anticipated Duration (Months)

14.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized controlled trial of different glycemic targets during tratment of women with GDM with assessement of epygenetic aspects of their effects on the fetus and pregnancy outcomes. This study is interventional, randomised controlled trialr, open-label.

Condition or Disease	Intervention/Treatment	Phase
Gestational Diabetes Mellitus	Other: Life-style modification, insulin therapy if needed Other: Life-style modification, insulin therapy if needed	N/A

Detailed Description

The study aims to clarify the effect of hyperglycemia and its correction, the level of physical activity and consumption of major macro- and micronutrients by women during pregnancy on DNA methylation and expression of genes involved in neuroendocrine regulation and development of metabolic diseases in offspring, as well as functional characteristics of human umbilical vein endothelial cells (HUVECs). For the purpose of the study women with GDM are randomised to 2 treatment groups per glycemic targets ( very tight and tight-moderate glycemic targets). Data on glycenmic levels during the study and consumption of major macro- and micronutrients will be collected using a mobile application with electronic dairies report forms.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

850 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Women with GDM are randomised to 2 treatment groups: group 1 - treatment group with very tight glycemic targets (<5.1 mmol / L fasting glucose and <7.0 mmol / l hour after a meal) and group 2 - treatment group with tight-moderate glycemic targets (<5.3 mmol / L fasting glucose and <7.8 mmol / l in an hour after a meal).Women with GDM are randomised to 2 treatment groups: group 1 - treatment group with very tight glycemic targets (<5.1 mmol / L fasting glucose and <7.0 mmol / l hour after a meal) and group 2 - treatment group with tight-moderate glycemic targets (<5.3 mmol / L fasting glucose and <7.8 mmol / l in an hour after a meal).

Masking:

Single (Investigator)

Primary Purpose:

Basic Science

Official Title:

Genetic and Epigenetic Mechanisms of Developing Gestational Diabetes Mellitus and Its Effects on the Fetus: a Randomised Controlled Trial of Different Glycemic Targets During Pregnancy

Actual Study Start Date :

Aug 1, 2015

Anticipated Primary Completion Date :

May 1, 2020

Anticipated Study Completion Date :

Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: very tight glycemic targets	Other: Life-style modification, insulin therapy if needed All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.1 mmol/L fasting and <7.0 mmol/L postprandial) are not achieved insulin therapy is started Other: Life-style modification, insulin therapy if needed All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.3 mmol/L fasting and <7.8 mmol/L postprandial) are not achieved insulin therapy is started
Active Comparator: tight-moderate glycemic targets	Other: Life-style modification, insulin therapy if needed All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.1 mmol/L fasting and <7.0 mmol/L postprandial) are not achieved insulin therapy is started Other: Life-style modification, insulin therapy if needed All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.3 mmol/L fasting and <7.8 mmol/L postprandial) are not achieved insulin therapy is started
No Intervention: Control group Only observation in women with normal glucose tolerance

Arm

Intervention/Treatment

Active Comparator: very tight glycemic targets

Other: Life-style modification, insulin therapy if needed

All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.1 mmol/L fasting and <7.0 mmol/L postprandial) are not achieved insulin therapy is started

Other: Life-style modification, insulin therapy if needed

All patients are assigned to life-style modification (diet and physical exercise). If target glucose levels (<5.3 mmol/L fasting and <7.8 mmol/L postprandial) are not achieved insulin therapy is started

Active Comparator: tight-moderate glycemic targets

Other: Life-style modification, insulin therapy if needed

No Intervention: Control group

Only observation in women with normal glucose tolerance

Outcome Measures

Primary Outcome Measures

LGA newborns [within 24 hours after delivery]
Number (%) of large for gestational age (LGA) newborns
TRIB1 [within 24 hours after delivery]
Level of expression of TRIB1 gene
LEP [within 24 hours after delivery]
Level of expression of LEP gene
ADIPOQ [within 24 hours after delivery]
Level of expression of ADIPOQ gene
ANGPTL4 [within 24 hours after delivery]
Level of expression of ANGPTL4 gene
NR3C1 [within 24 hours after delivery]
Level of expression of NR3C1 gene

Secondary Outcome Measures

Cesarian sections [within 24 hours after delivery]
Number (%) of deliveries by Cesarian sections
SGA newborns [within 24 hours after delivery]
Number (%) of small for gestationa age (SGA) newborns
Methylation of candidate genes [within 24 hours after delivery]
Levels of methylation (%) of candidate genes with confirmed differences in the expression in HUVECs isolated within 24 hours after delivery

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Pregnant women with GDM diagnosed according to the Russian national consensus and the recommendations of the International Association of Diabetes and Pregnancy Study Groups (fasting glucose of ≥5.1 mmol/L, and/or ≥10.0 mmol/L after 1 h, and/or ≥8.5 mmol/L after 2 h in oral glucose tolerance test (OGTT) with 75 g of glucose).
Gestational age at the time of inclusion in the study 12 weeks 0 days - 31 weeks 6 days
For control group: pregnant women with normal glucose tolerance confirmed by OGTT at 24-31 weeks of gestation.

Exclusion Criteria:

Diabetes mellitus type 1 and tipe 2
Other deseases that affect methabolism of carbohydrates
Use of drugs that affect methabolism of carbohydrates
Malformations of the fetus identifired prior to inclusion to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Almazov NMRC	Saint Petersburg		Russian Federation	197341

Sponsors and Collaborators

Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Investigators

Study Director: Griniva Elena, MD, PhD, Almazov NMRC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

ClinicalTrials.gov Identifier:

NCT03610178

Other Study ID Numbers:

15-14-30012

First Posted:

Aug 1, 2018

Last Update Posted:

Feb 12, 2020

Last Verified:

Feb 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes, Gestational

Diabetes Mellitus

Insulin

Insulin, Globin Zinc

Study Results

No Results Posted as of Feb 12, 2020