Congenital Heart Anomaly Risk in Maternal Enteroviral Infection and Diabetes — CHARMED  

Diabetes Mellitus, Type 2 Clinical Trial

Official title: Congenital Heart Anomaly Risk in Maternal Enteroviral Infection and Diabetes

Status Active, not recruiting

Clinical Trial Summary

Beyond EV-B, there are clinical observations to implicate other viruses in birth defects, including CHD. Since the Rubella epidemic of 1960s', however, viruses have received little attention and certainly no comprehensive study, especially using next generation sequencing (NGS), has been undertaken in this context. The current pandemic as well as those caused by Zika, influenza, Ebola and Lassa Fever (among many) have shown pregnant women and their baby are at high risk. Therefore, an open-minded approach is warranted when considering the role of maternal viral infections in CHD. Even less is known about maternal immune response, such as antibody production, to these viruses.

The investigator's goal is to answer the above gaps in knowledge. The investigators propose to do that using two different approaches; one retrospective (analysis of samples in two existing, large biorepositories) and the other prospective. The investigator's have created a multi-disciplinary team to bring together the needed expertise from individuals who have overlapping and vested interest in this project.

The investigator's specific aim is to examine the diversity of the gut virome in non-pregnant and pregnant women with and without diabetes, with special emphasis on known cardiotropic viruses (those with tropism for cardiac tissues). This study is seen by the investigator's as the first step prior to a larger prospective multi-institutional study to specifically assess the linkage between the maternal virome and CHD pathogenesis.

Clinical Trial Description

To determine prevalence in non-pregnant women (i) the investigators will perform PCR analysis of stool and blood from a prospective cohort of 225 women with diabetes (and 225 without) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected concurrently. They will assay IgM/IgG positive samples for neutralizing antibodies. To determine prevalence in pregnant women (i) the investigators will perform PCR analysis of 1st trimester stool and blood from a prospective cohort of 450 women with diabetes (and 450 without diabetes) and sequence the amplicons, and (ii) perform ELISA (IgM and IgG) analysis of sera collected at 1st and 2nd or 3rd trimester. They will assay IgM/IgG positive samples for neutralizing antibodies.

The investigators will also perform a comprehensive virome analysis using metagenomic shotgun sequencing with ViroCap enrichment, a method developed by co-PI, on 1st trimester stool samples from a subset (~4-500) of women (both EVB positive and negative) enrolled in Aim 1. The investigators will complement this data with VirScan® analysis of blood collected from the same women at 1st and 2nd/3rd trimester. VirScan® is a revolutionary new technique for comprehensive profiling of sera for antibodies against ~400 species and strains of pathogenic viruses. ;

Related Conditions & MeSH terms

• Communicable Diseases
• Congenital Abnormalities
• Congenital Heart Disease
• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Enterovirus
• Enterovirus Infections
• Heart Defects, Congenital
• Heart Diseases
• Infections
• Pregnancy Complications
• Pregnancy in Diabetic
• Pregnancy in Diabetics
• Prenatal
• Prenatal Infection
• Viremia
• Virus Diseases

• NCT number: NCT04769167
• Study type: Interventional
• Source: Washington University School of Medicine
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 1, 2021
• Completion date: December 2027