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

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

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.

Study Overview

• Status: Unknown
• Conditions: Gestational Diabetes Mellitus
• Intervention / Treatment: Other: Life-style modification, insulin therapy if needed; Other: Life-style modification, insulin therapy if needed

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 Type: Interventional
• Enrollment (Anticipated): 850
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Polina Popova, MD, PhD; Phone Number: +78127550595; Email: pvpopova@yandex.ru

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197341
    • Recruiting
    • Almazov NMRC
    • Contact: Polina Popova, MD, PhD; Phone Number: +78127025595; Email: pvpopova@yandex.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LGA newborns	Number (%) of large for gestational age (LGA) newborns	within 24 hours after delivery
TRIB1	Level of expression of TRIB1 gene	within 24 hours after delivery
LEP	Level of expression of LEP gene	within 24 hours after delivery
ADIPOQ	Level of expression of ADIPOQ gene	within 24 hours after delivery
ANGPTL4	Level of expression of ANGPTL4 gene	within 24 hours after delivery
NR3C1	Level of expression of NR3C1 gene	within 24 hours after delivery

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2015
• Primary Completion (ANTICIPATED): May 1, 2020
• Study Completion (ANTICIPATED): July 1, 2020

Study Registration Dates

• First Submitted: November 13, 2017
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (ACTUAL): August 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Pregnancy Complications; Diabetes Mellitus; Diabetes, Gestational; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 15-14-30012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No